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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Vascular smooth muscle cells (VSMCs), the contractile cells in the tunica media of blood vessels, maintain vascular tone. The proliferation of VSMCs is an important feature of vascular remodeling that contributes to the regulation of blood pressure. Autophagy, an intracellular self-degrading process that delivers cytoplasmic constituents to lysosomes, plays a vital role in VSMC proliferation. This is regulated by the dopaminergic and renin\u2013angiotensin systems but their interplay in their regulation of autophagy in VSMCs is not well-understood. In rat VSMCs, fenoldopam (Fen), a dopamine D1-like receptor agonist, increased autophagy, as determined by the increase in the protein expressions of microtubule-associated protein 1 light chain (LC)3-II and beclin-1 (BECN1), in a time- and concentration-dependent manner. Conversely, angiotensin II (Ang II), the endogenous Ang II type 1 receptor (AT1R) agonist, decreased the protein expression of LC3-II and BECN1, also in a time- and concentration-dependent manner. The production of cyclic adenosine monophosphate (cAMP) and autophagic LC3-II puncta in VSMCs were increased by Fen and decreased by Ang II. Pre-treatment of VSMCs with Rp-cAMPS, a protein kinase A inhibitor, prevented the Fen-mediated increase and the Ang II-mediated decrease in LC3-II protein expression. Fen decreased, whereas Ang II increased the phosphorylation of P70S6K, a direct downstream mammalian target of rapamycin (mTOR). The inhibitory effect of Fen and stimulatory effect of Ang II on P70S6K phosphorylation were prevented by Rp-cAMPS. Ang II also decreased the Fen-mediated increase in cAMP production, while Fen attenuated the Ang II-mediated increase in cell proliferation, a response that occurs downstream of autophagy. Moreover, Ang II prevented the Fen-mediated inhibition of cell proliferation, an effect that was blocked by losartan, an AT1R antagonist. These results demonstrate that Fen and Ang II counter-regulate autophagy and proliferation of VSMCs via the mTOR pathway, which is cAMP-dependent.<\/jats:p>","DOI":"10.3390\/ijms27156784","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:13:47Z","timestamp":1785320027000},"page":"6784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dopamine D1-like and Angiotensin II Type 1 Receptors Counter-Regulate Autophagy and Cell Proliferation in Rat Embryonic Thoracic Vascular Smooth Muscle Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1338-2573","authenticated-orcid":false,"given":"Hewang","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Kidney Disease & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"},{"name":"Department of 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Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8202-0432","authenticated-orcid":false,"given":"Jacob","family":"Polzin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Kidney Disease & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maithri","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Kidney Disease & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raisha C.","family":"Cadme","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Kidney Disease & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2797-4289","authenticated-orcid":false,"given":"Robin A.","family":"Felder","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Armando","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Kidney Disease & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"},{"name":"Department of Pharmacology and Physiology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"},{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA"},{"name":"Center for Molecular Physiology Research, Children\u2019s National Research Institute, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9052-186X","authenticated-orcid":false,"given":"Jeffrey B.","family":"Kopp","sequence":"additional","affiliation":[{"name":"Independent Researcher, 2324 North Apple Lane, Pocatello, ID 83204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"Jose","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Kidney Disease & Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA"},{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA"},{"name":"Center for Molecular Physiology Research, Children\u2019s National Research Institute, Washington, DC 20010, 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Cell. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/14728222.2020.1723079","article-title":"Autophagy as an emerging therapeutic target for age-related vascular pathologies","volume":"24","author":"Martinet","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/j.2040-4603.2011.tb00359.x","article-title":"Dopamine and renal function and blood pressure regulation","volume":"1","author":"Armando","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00281-020-00819-8","article-title":"Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation","volume":"42","author":"Campos","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1042\/CS20220338","article-title":"Interactions between the intrarenal dopaminergic and the renin-angiotensin systems in the control of systemic arterial pressure","volume":"136","author":"Jose","year":"2022","journal-title":"Clin. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1124\/pharmrev.122.000618","article-title":"Dopamine, immunity, and disease","volume":"75","author":"Channer","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yang, J., and Jose, P.A. (2026). Role of Renal Dopamine Receptors in the Regulation of Blood Pressure. Biomolecules, 16.","DOI":"10.3390\/biom16040532"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3109\/10641963.2013.789048","article-title":"Dopamine d(1)-like receptors suppress proliferation of vascular smooth muscle cell induced by insulin-like growth factor-1","volume":"36","author":"Kou","year":"2014","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","article-title":"Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology","volume":"98","author":"Forrester","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1006\/bbrc.1998.9505","article-title":"Involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in AII-mediated enhanced expression of Gi proteins in vascular smooth muscle cells","volume":"251","author":"Ge","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-022-00542-2","article-title":"The mechanisms and roles of selective autophagy in mammals","volume":"24","author":"Vargas","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41440-021-00646-w","article-title":"Dopamine D5 receptor-mediated decreases in mitochondrial reactive oxygen species production are cAMP and autophagy dependent","volume":"44","author":"Lee","year":"2021","journal-title":"Hypertens. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cell.2014.11.047","article-title":"Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome","volume":"160","author":"Yan","year":"2015","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.omtn.2020.06.015","article-title":"Salvia miltiorrhiza-derived Sal-miR-58 induces autophagy and attenuates inflammation in vascular smooth muscle cells","volume":"21","author":"Qin","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s00395-014-0416-y","article-title":"Mitochondrial KATP channel involvement in angiotensin II-induced autophagy in vascular smooth muscle cells","volume":"109","author":"Yu","year":"2014","journal-title":"Basic Res. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jphs.2020.12.001","article-title":"Activation of the angiotensin II receptor promotes autophagy in renal proximal tubular cells and affords protection from ischemia\/reperfusion injury","volume":"145","author":"Sugawara","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00064","DOI":"10.1002\/phy2.64","article-title":"Aldosterone and angiotensin II induce protein aggregation in renal proximal tubules","volume":"1","author":"Cheema","year":"2013","journal-title":"Physiol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1038\/s41418-021-00761-8","article-title":"PKA compartmentalization links cAMP signaling and autophagy","volume":"28","author":"Grisan","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s41440-020-00552-7","article-title":"Acute infusion of angiotensin II regulates organic cation transporters function in the kidney: Its impact on the renal dopaminergic system and sodium excretion","volume":"44","author":"Kouyoumdzian","year":"2021","journal-title":"Hypertens. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1172\/JCI33637C1","article-title":"Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells","volume":"118","author":"Li","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1681\/ASN.2011040344","article-title":"Binding of losartan to angiotensin AT1 receptors increases dopamine D1 receptor activation","volume":"23","author":"Li","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41390-019-0716-x","article-title":"Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness","volume":"87","author":"Crockett","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1080\/15548627.2022.2039535","article-title":"Chloroquine treatment induces secretion of autophagy-related proteins and inclusion of Atg8-family proteins in distinct extracellular vesicle populations","volume":"18","author":"Xu","year":"2022","journal-title":"Autophagy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1152\/japplphysiol.00898.2018","article-title":"Angiotensin II suppresses autophagy and disrupts ultrastructural morphology and function of mitochondria in mouse skeletal muscle","volume":"126","author":"Silva","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1046\/j.1523-1755.2000.00217.x","article-title":"Diminished natriuretic response to dopamine in old rats is due to an impaired D1-like receptor-signaling pathway","volume":"58","author":"Beheray","year":"2000","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1080\/15548627.2022.2125204","article-title":"cAMP-Protein kinase A and stress-activated MAP kinase signaling mediate transcriptional control of autophagy in fission yeast during glucose limitation or starvation","volume":"19","author":"Soto","year":"2023","journal-title":"Autophagy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C559","DOI":"10.1152\/ajpcell.00123.2011","article-title":"Intracellular angiotensin II activates rat myometrium","volume":"301","author":"Deliu","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"C768","DOI":"10.1152\/ajpcell.00191.2016","article-title":"Angiotensin II counteracts the effects of cAMP\/PKA on NHE3 activity and phosphorylation in proximal tubule cells","volume":"311","author":"Crajoinas","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0022-3565(25)23583-2","article-title":"Increase of cyclic AMP concentrations in cultured vascular smooth muscle cells by vasoactive peptide hormones. Role of endogenous prostaglandins","volume":"239","author":"Hassid","year":"1986","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1159\/000487562","article-title":"Angiotensin II regulates Th1 T cell differentiation through angiotensin II type 1 receptor-PKA-mediated activation of proteasome","volume":"45","author":"Qin","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1097\/HJH.0b013e3283293c7b","article-title":"D1-like receptors inhibit insulin-induced vascular smooth muscle cell proliferation via down-regulation of insulin receptor expression","volume":"27","author":"Zeng","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/cvr\/cvu242","article-title":"Exchange protein directly activated by cAMP 1 promotes autophagy during cardiomyocyte hypertrophy","volume":"105","author":"Laurent","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e43038","DOI":"10.7554\/eLife.43038","article-title":"GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor","volume":"8","author":"Jewell","year":"2019","journal-title":"eLife"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, H., Song, A., Hu, W., and Dai, M. (2018). The anti-atherosclerotic effect of paeonol against vascular smooth muscle cell proliferation by up-regulation of autophagy via the AMPK\/mTOR signaling pathway. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00948"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1080\/15548627.2019.1668606","article-title":"DRD3 (dopamine receptor D3) but not DRD2 activates autophagy through MTORC1 inhibition preserving protein synthesis","volume":"16","year":"2020","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1126\/science.aaa3870","article-title":"Architecture of human mTOR complex 1","volume":"351","author":"Aylett","year":"2016","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1080\/15548627.2021.2021494","article-title":"Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy","volume":"18","author":"Tripathi","year":"2022","journal-title":"Autophagy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1161\/CIRCRESAHA.119.314062","article-title":"Protective role of RNA helicase DEAD-Box protein 5 in smooth muscle cell proliferation and vascular remodeling","volume":"124","author":"Fan","year":"2019","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s00424-020-02408-y","article-title":"Defective autophagy in vascular smooth muscle cells increases passive stiffness of the mouse aortic vessel wall","volume":"472","author":"Leloup","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neuropharm.2019.01.023","article-title":"Multiple molecular pathways stimulating macroautophagy protect from alpha-synuclein-induced toxicity in human neurons","volume":"149","author":"Fussi","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10801","DOI":"10.1523\/JNEUROSCI.22-24-10801.2002","article-title":"Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive","volume":"22","author":"Hollon","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1172\/JCI118670","article-title":"Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension","volume":"97","author":"Albrecht","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.ccell.2016.05.002","article-title":"Inhibition of dopamine receptor D4 impedes autophagic flux, proliferation, and survival of glioblastoma stem cells","volume":"29","author":"Dolma","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, D., Ji, X., Liu, J., Li, Z., and Zhang, X. (2018). Dopamine receptor subtypes differentially regulate autophagy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051540"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00213-022-06097-6","article-title":"Dopamine D1 receptors mediate methamphetamine-induced dopaminergic damage: Involvement of autophagy regulation via the AMPK\/FOXO3A pathway","volume":"239","author":"He","year":"2022","journal-title":"Psychopharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"929","DOI":"10.4161\/auto.6.7.12785","article-title":"Quantitation of \u201cautophagic flux\u201d in mature skeletal muscle","volume":"6","author":"Ju","year":"2010","journal-title":"Autophagy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1293\/tox.2024-0104","article-title":"Influence of rapamycin and chloroquine on chemically-induced liver injury in rats","volume":"39","author":"Fujiwara","year":"2026","journal-title":"J. Toxicol. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","article-title":"mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt","volume":"66","author":"Rojo","year":"2006","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"36112","DOI":"10.1074\/jbc.M703914200","article-title":"Rapamycin promotes vascular smooth muscle cell differentiation through insulin receptor substrate-1\/phosphatidylinositol 3-kinase\/Akt2 feedback signaling","volume":"282","author":"Martin","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.freeradbiomed.2013.08.003","article-title":"Implications of autophagy for vascular smooth muscle cell function and plasticity","volume":"65","author":"Salabei","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"36662","DOI":"10.1074\/jbc.M606676200","article-title":"Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP","volume":"281","author":"Hurley","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/15548627.2015.1055440","article-title":"Feedback regulation between autophagy and PKA","volume":"11","author":"Filteau","year":"2015","journal-title":"Autophagy"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Aslam, M., and Ladilov, Y. (2022). Emerging role of cAMP\/AMPK signaling. Cells, 11.","DOI":"10.3390\/cells11020308"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Mondaca-Ruff, D., Riquelme, J.A., Quiroga, C., Norambuena-Soto, I., Sanhueza-Olivares, F., Villar-Fincheira, P., Hern\u00e1ndez-D\u00edaz, T., Cancino-Arenas, N., San Martin, A., and Garc\u00eda, L. (2019). Angiotensin II-regulated autophagy is required for vascular smooth muscle cell hypertrophy. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01553"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1248\/bpb.b19-00053","article-title":"Tanshinone IIA can inhibit angiotensin II-induced proliferation and autophagy of vascular smooth muscle cells via regulating the MAPK signaling pathway","volume":"42","author":"Lu","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1161\/HYPERTENSIONAHA.119.12705","article-title":"The Dopamine D1 Receptor and Angiotensin II Type-2 Receptor are Required for Inhibition of Sodium Transport Through a Protein Phosphatase 2A Pathway","volume":"73","author":"Gildea","year":"2019","journal-title":"Hypertension"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1124\/pharmrev.120.000281","article-title":"The Angiotensin AT2 Receptor: From a Binding Site to a Novel Therapeutic Target","volume":"74","author":"Steckelings","year":"2022","journal-title":"Pharmacol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1073\/pnas.92.23.10663","article-title":"The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: Gain-of-function study using gene transfer","volume":"92","author":"Nakajima","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","first-page":"249","article-title":"Overexpression of angiotensin II type 2 receptor suppresses neointimal hyperplasia in a rat carotid arterial balloon injury model","volume":"4","author":"Tang","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e14134","DOI":"10.1111\/apha.14134","article-title":"Unraveling the crosstalk between renin-angiotensin system receptors","volume":"240","author":"Gironacci","year":"2024","journal-title":"Acta Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41419-020-2326-2","article-title":"A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy","volume":"11","author":"Wu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16645","DOI":"10.1096\/fj.202001494R","article-title":"Sirtuin 3 governs autophagy-dependent glycolysis during Angiotensin II-induced endothelial-to-mesenchymal transition","volume":"34","author":"Gao","year":"2020","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/iep.12427","article-title":"NLRC5 enhances autophagy via inactivation of AKT\/mTOR pathway and ameliorates cardiac hypertrophy","volume":"103","author":"Ba","year":"2022","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e574","DOI":"10.1002\/ctm2.574","article-title":"Bmi-1-RING1B prevents GATA4-dependent senescence-associated pathological cardiac hypertrophy by promoting autophagic degradation of GATA4","volume":"12","author":"Chen","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"De Munck, D.G., De Moudt, S., Roth, L., De Meyer, G.R.Y., Martinet, W., and Fransen, P. (2020). Defective autophagy in vascular smooth muscle cells alters vascular reactivity of the mouse femoral artery. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.548943"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"115384","DOI":"10.1016\/j.bcp.2022.115384","article-title":"Role of Gi proteins in the regulation of blood pressure and vascular remodeling","volume":"208","author":"Li","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nchembio.1766","article-title":"Dual agonist occupancy of AT1R-\u03b12CAR heterodimers results in atypical Gs-PKA signaling","volume":"11","author":"Bellot","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ncb2329","article-title":"The AMPK signalling pathway coordinates cell growth, autophagy and metabolism","volume":"13","author":"Mihaylova","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1164\/rccm.201911-2137OC","article-title":"Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling","volume":"201","author":"He","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"15192","DOI":"10.1074\/jbc.M009130200","article-title":"Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79","volume":"276","author":"Cong","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1007\/s00018-019-03274-3","article-title":"G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub","volume":"76","author":"Penela","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.pharmthera.2010.05.003","article-title":"Pharmacology of signaling induced by dopamine D(1)-like receptor activation","volume":"128","author":"Undieh","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1478-811X-10-17","article-title":"Role of the inositol 1,4,5-trisphosphate receptor\/Ca2+-release channel in autophagy","volume":"10","author":"Parys","year":"2012","journal-title":"Cell Commun. Signal."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e70361","DOI":"10.1002\/ctm2.70361","article-title":"DDR2-mediated autophagy inhibition contributes to angiotensin II-induced adventitial remodeling","volume":"15","author":"Huang","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Deng, M., Su, D., Xu, S., Little, P.J., Feng, X., Tang, L., and Shen, A. (2020). Metformin and vascular diseases: A focused review on smooth muscle cell function. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00635"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000534929","article-title":"Impairment of autophagy mediates the uric-acid-induced phenotypic transformation of vascular smooth muscle cells","volume":"109","author":"Lu","year":"2024","journal-title":"Pharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3892\/etm.2022.11243","article-title":"Vitamin D receptor deficiency increases systolic blood pressure by upregulating the renin-angiotensin system and autophagy","volume":"23","author":"Jia","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"115643","DOI":"10.1016\/j.biopha.2023.115643","article-title":"Unveiling the dual role of autophagy in vascular remodelling and its related diseases","volume":"168","author":"Ren","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e13688","DOI":"10.1111\/cpr.13688","article-title":"Regulated vascular smooth muscle cell death in vascular diseases","volume":"57","author":"Yin","year":"2024","journal-title":"Cell Prolif."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1016\/j.numecd.2023.07.026","article-title":"Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study","volume":"33","author":"Tocci","year":"2023","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1161\/CIRCRESAHA.116.303804","article-title":"Autophagy in vascular disease","volume":"116","author":"Grootaert","year":"2015","journal-title":"Circ. Res."},{"key":"ref_85","first-page":"e13","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"71","author":"Whelton","year":"2018","journal-title":"Hypertension"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2147\/VHRM.S337640","article-title":"Angiotensin receptor blockers in the management of hypertension: A real-world perspective and current recommendations","volume":"18","author":"Gallo","year":"2022","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/BF00315201","article-title":"A single dose study of the effects of fenoldopam and enalapril in mild hypertension","volume":"40","author":"MacDonald","year":"1991","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s43587-022-00322-9","article-title":"Mechanisms of spermidine-induced autophagy and geroprotection","volume":"2","author":"Hofer","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"503","DOI":"10.2174\/1389203724666230606154719","article-title":"Trehalose and its diverse biological potential","volume":"24","author":"Sharma","year":"2023","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1161\/01.HYP.36.3.395","article-title":"Dopamine1 receptor, GS\u03b1, and Na+-H+ exchanger interactions in the kidney in hypertension","volume":"36","author":"Xu","year":"2000","journal-title":"Hypertension"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ahmed, S., Johnson, R.T., Solanki, R., Afewerki, T., Wostear, F., and Warren, D.T. (2022). Using polyacrylamide hydrogels to model physiological aortic stiffness reveals that microtubules are critical regulators of isolated smooth muscle cell morphology and contractility. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.836710"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1161\/ATVBAHA.118.311229","article-title":"Vascular smooth muscle remodeling in conductive and resistance arteries in hypertension","volume":"38","author":"Brown","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"H2761","DOI":"10.1152\/ajpheart.01344.2007","article-title":"Inhibitory effect of D1-like and D3 dopamine receptors on norepinephrine-induced proliferation in vascular smooth muscle cells","volume":"294","author":"Li","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"056003","DOI":"10.1117\/1.3484751","article-title":"Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy","volume":"15","author":"Li","year":"2010","journal-title":"J. Biomed. Opt."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Shrivastav, S., Lee, H., Okamoto, K., Lu, H., Yoshida, T., Latt, K.Z., Wakashin, H., Dalgleish, J.L.T., Koritzinsky, E.H., and Xu, P. (2022). HIV-1 Vpr suppresses expression of the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0273313"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nature08455","article-title":"Discovery of Atg5\/Atg7-independent alternative macroautophagy","volume":"461","author":"Nishida","year":"2009","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cell.2011.06.023","article-title":"Autophagosome precursor maturation requires homotypic fusion","volume":"146","author":"Moreau","year":"2011","journal-title":"Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6784\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:28:58Z","timestamp":1785472138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":97,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156784"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156784","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]}}}