{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:56:58Z","timestamp":1785405418935,"version":"3.56.0"},"reference-count":93,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008967","name":"Philipps-Universit\u00e4t Marburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008967","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as an anti-atherogenic neuropeptide. Maxadilan, a PAC1 receptor agonist, offers atheroprotection by acting downstream of vascular inflammation caused by hypercholesterolemia. This study aims to explore how PACAP and Maxadilan influence migration and apoptosis in human coronary artery smooth muscle cells (HCASMCs). Methods: To investigate the role of PACAP deficiency in the pathogenesis of atherosclerosis under standard chow (SC) in vivo, PACAP\u2212\/\u2212-mice were crossed with ApoE\u2212\/\u2212-mice to generate PACAP\u2212\/\u2212\/ApoE\u2212\/\u2212-mice. The whole aorta was isolated and stained with OilRedO (ORO). Atherosclerotic lesions and lumen stenosis in the brachiocephalic trunk were quantified using ImageJ 1.54p (Fiji). To further investigate the role of PACAP and Maxadilan in the pathogenesis of atherosclerosis with special respect to HCASMC under a lipid-enriched environment, HCASMCs were treated with oxLDL, with or without PACAP or Maxadilan. Uptake and accumulation of oxLDL were analyzed using BodipyTM493\/503, and cell viability was assessed with PrestoBlue\u00ae. Cell migration was evaluated using the scratch assay and the MRI wound-healing tool in ImageJ (Fiji). Mitochondrial morphology was examined with MitoTracker Green and the MiNA tool in ImageJ (Fiji). Apoptotic processes were analyzed by Western blot, immunocytofluorescence staining, and ELISA. Results: In vivo, PACAP\u2212\/\u2212\/ApoE\u2212\/\u2212-mice showed increased lumen stenosis and decreased plaque burden compared with ApoE\u2212\/\u2212-mice. In vitro, PACAP enhanced the viability of oxLDL-treated HCASMCs, while neither PACAP nor Maxadilan influenced lipid content in HCASMCs, regardless of oxLDL presence. Both oxLDL and PACAP slowed cell migration, but Maxadilan increased migration in oxLDL-treated HCASMCs. The protein level of the proliferation marker Ki67 was reduced in cells treated with oxLDL and Maxadilan. Additionally, BAX, which promotes intrinsic apoptosis, was elevated in HCASMCs stimulated with Maxadilan and oxLDL. Investigations of mitochondrial morphology indicated that oxLDL and PACAP increased the individual and network structures, with a decrease in branches per network. Conclusion: Our data highlight the complex role of the PACAP\/PAC1 system in vascular pathology and suggest that selective modulation\u2014such as targeted PAC1 activation or PACAP supplementation\u2014could lead to new strategies for stabilizing atherosclerotic plaques. In the long term, this could improve the balance between plaque formation and vascular function.<\/jats:p>","DOI":"10.3390\/cells15121127","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PACAP and Maxadilan (PAC1 Agonist) Influence Plaque Progression, Migratory Ability, and Mitochondrial Morphology and Dynamics in Vascular Smooth Muscle Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Julia","family":"Brauschke","sequence":"first","affiliation":[{"name":"Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, Philipps-University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Marie","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Department of Public Health and Environmental Health, Apollon University of Applied Sciences, 28359 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel A.","family":"Bonaterra","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, Philipps-University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Kinscherf","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, Philipps-University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9567-0717","authenticated-orcid":false,"given":"Anja","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, Philipps-University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2013). Global Action Plan for the Prevention and Control of Noncommunicable Diseases, 2013\u20132020, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","article-title":"Mechanisms of plaque formation and rupture","volume":"114","author":"Bentzon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular Smooth Muscle Cells in Atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jarad, S., Gill, G., Amadi, P., Gu, H.-M., and Zhang, D.-W. (2025). VSMCs in Atherosclerosis: Implications on the Role of Inflammation and Extracellular Matrix Remodelling. Pharmacol. Res., 218.","DOI":"10.1016\/j.phrs.2025.107833"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/01.ATV.18.3.333","article-title":"Smooth muscle cell heterogeneity: Patterns of gene expression in vascular smooth muscle cells in vitro and in vivo","volume":"18","author":"Shanahan","year":"1998","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_6","first-page":"15","article-title":"Molecular mechanism of phenotypic modulation of smooth muscle cells","volume":"50","author":"Sobue","year":"1998","journal-title":"Horm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1161\/CIRCRESAHA.116.309799","article-title":"Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models","volume":"119","author":"Chappell","year":"2016","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41569-019-0227-9","article-title":"Vascular smooth muscle cells in atherosclerosis","volume":"16","author":"Basatemur","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nm.3866","article-title":"KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis","volume":"21","author":"Shankman","year":"2015","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41591-019-0512-5","article-title":"Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis","volume":"25","author":"Wirka","year":"2019","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/CIRCULATIONAHA.120.046672","article-title":"Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis","volume":"142","author":"Alencar","year":"2020","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1161\/CIRCULATIONAHA.120.048378","article-title":"Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human","volume":"142","author":"Pan","year":"2020","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.atherosclerosis.2021.03.034","article-title":"Targeting the phenotypic switch of vascular smooth muscle cells to tackle atherosclerosis","volume":"324","author":"Kansakar","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1161\/CIRCULATIONAHA.113.005015","article-title":"Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis","volume":"129","author":"Allahverdian","year":"2014","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1161\/ATVBAHA.119.312434","article-title":"Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis","volume":"39","author":"Wang","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0006-291X(89)91757-9","article-title":"Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells","volume":"164","author":"Miyata","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0031-6997(24)01449-2","article-title":"Pituitary adenylate cyclase-activating polypeptide and its receptors: From structure to functions","volume":"52","author":"Vaudry","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0167-0115(02)00099-X","article-title":"Molecular pharmacology and structure of VPAC Receptors for VIP and PACAP","volume":"108","author":"Laburthe","year":"2002","journal-title":"Regul. Pept."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1476-5381.2012.01871.x","article-title":"Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1","volume":"166","author":"Harmar","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1006\/bbrc.1994.1517","article-title":"Human intestinal VIP receptor: Cloning and functional expression of two cDNA encoding proteins with different N-terminal domains","volume":"200","author":"Couvineau","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.imbio.2018.09.008","article-title":"PACAP deficiency aggravates atherosclerosis in ApoE deficient mice","volume":"224","author":"Rasbach","year":"2019","journal-title":"Immunobiology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Witzel, R., Block, A., Pollmann, S., Oetzel, L., Fleck, F., Bonaterra, G.A., Kinscherf, R., and Schwarz, A. (2023). PACAP regulates VPAC1 expression, inflammatory processes and lipid homeostasis in M1- and M2-macrophages. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1264901"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Splitthoff, P., Rasbach, E., Neudert, P., Bonaterra, G.A., Schwarz, A., Mey, L., Schwarzbach, H., Eiden, L.E., Weihe, E., and Kinscherf, R. (2020). PAC1 deficiency attenuates progression of atherosclerosis in ApoE deficient mice under cholesterol-enriched diet. Immunobiology, 225.","DOI":"10.1016\/j.imbio.2020.151930"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1074\/jbc.272.2.966","article-title":"Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist","volume":"272","author":"Moro","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mey, L., Bonaterra, G.A., Hoffmann, J., Schwarzbach, H., Schwarz, A., Eiden, L.E., Weihe, E., and Kinscherf, R. (2024). PAC1 Agonist Maxadilan Reduces Atherosclerotic Lesions in Hypercholesterolemic ApoE-Deficient Mice. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202410.0941.v1"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Juh\u00e1sz, T., Matta, C., Katona, \u00c9., Somogyi, C., Tak\u00e1cs, R., Gergely, P., Csernoch, L., Panyi, G., T\u00f3th, G., and Regl\u0151di, D. (2014). Pituitary adenylate cyclase activating polypeptide (PACAP) signalling exerts chondrogenesis promoting and protecting effects: Implication of calcineurin as a downstream target. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091541"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s12031-014-0389-1","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP) signalling enhances osteogenesis in UMR-106 cell line","volume":"54","author":"Matta","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bl\u00fcmm, C., Bonaterra, G.A., Schwarzbach, H., Eiden, L.E., Weihe, E., and Kinscherf, R. (2023). PAC1 deficiency reduces chondrogenesis in atherosclerotic lesions of hypercholesterolemic ApoE-deficient mice. BMC Cardiovasc. Disord., 23.","DOI":"10.1186\/s12872-023-03600-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1073\/pnas.012608999","article-title":"Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis","volume":"99","author":"Hamelink","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gargiulo, S., Gramanzini, M., Megna, R., Greco, A., Albanese, S., Manfredi, C., and Brunetti, A. (2014). Evaluation of growth patterns and body composition in C57Bl\/6J mice using dual energy X-ray absorptiometry. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/253067"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, P.-Y., Qin, L., and Simons, M. (2022). Imaging and Analysis of Oil Red O-Stained Whole Aorta Lesions in an Aneurysm Hyperlipidemia Mouse Model. J. Vis. Exp., 183.","DOI":"10.3791\/61277-v"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1096\/fasebj.11.14.9409551","article-title":"Induction of mitochondrial manganese superoxide dismutase in macrophages by oxidized LDL: Its relevance in atherosclerosis of humans and heritable hyperlipidemic rabbits","volume":"11","author":"Kinscherf","year":"1997","journal-title":"FASEB J."},{"key":"ref_34","first-page":"119","article-title":"Oxidized LDL and Lp(a). Preparation, modification, and analysis","volume":"108","author":"Galle","year":"1998","journal-title":"Methods Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1016\/S0021-9258(18)61395-X","article-title":"Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products","volume":"262","author":"Steinbrecher","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_36","unstructured":"Foxx, K.K., Roberts, R.L., and Waxdal, M.J. (2008). Effect of Copper Ion Concentration on the Oxidation of Human LDL, Kalen Biomedical, LLC."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11798","DOI":"10.1074\/jbc.271.20.11798","article-title":"Mechanism of uptake of copper-oxidized low density lipoprotein in macrophages is dependent on its extent of oxidation","volume":"271","author":"Lougheed","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.vascn.2013.09.003","article-title":"Comparison of PrestoBlue and MTT assays of cellular viability in the assessment of anti-proliferative effects of plant extracts on human endothelial cells","volume":"69","author":"Boncler","year":"2014","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1146\/annurev-biochem-061009-102430","article-title":"Lipid Droplets and Cellular Lipid Metabolism","volume":"81","author":"Walther","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.acthis.2017.03.001","article-title":"A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture","volume":"119","author":"Valente","year":"2017","journal-title":"Acta Histochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2818.1993.tb03313.x","article-title":"Measurement of co-localization of objects in dual-colour confocal images","volume":"169","author":"Manders","year":"1993","journal-title":"J. Microsc."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bakare, A.B., Daniel, J., Stabach, J., Rojas, A., Bell, A., Henry, B., and Iyer, S. (2021). Quantifying Mitochondrial Dynamics in Patient Fibroblasts with Multiple Developmental Defects and Mitochondrial Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126263"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kiryu-Seo, S., Tamada, H., Kato, Y., Yasuda, K., Ishihara, N., Nomura, M., Mihara, K., and Kiyama, H. (2016). Mitochondrial fission is an acute and adaptive response in injured motor neurons. Sci. Rep., 6.","DOI":"10.1038\/srep28331"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zemirli, N., Morel, E., and Molino, D. (2018). Mitochondrial Dynamics in Basal and Stressful Conditions. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020564"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10190","DOI":"10.1073\/pnas.1107402108","article-title":"Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation","volume":"108","author":"Rambold","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tem.2015.12.001","article-title":"Mitochondrial Dynamics and Metabolic Regulation","volume":"27","author":"Wai","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_47","first-page":"132","article-title":"Experimental study of the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and its mechanism on the vascular cell components\u2014The possible relationship between PACAP and atherosclerosis","volume":"28","author":"Chang","year":"1997","journal-title":"Sheng Li Ke Xue Jin Zhan"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.peptides.2005.06.022","article-title":"Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis","volume":"27","author":"Gasz","year":"2006","journal-title":"Peptides"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1523\/JNEUROSCI.4999-12.2013","article-title":"Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability","volume":"33","author":"Merriam","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s11883-003-0088-9","article-title":"Coronary arterial remodeling: From bench to bedside","volume":"5","author":"Schoenhagen","year":"2003","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1056\/NEJM198705283162204","article-title":"Compensatory enlargement of human atherosclerotic coronary arteries","volume":"316","author":"Glagov","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1161\/01.CIR.0000147235.53360.59","article-title":"Pulmonary hypertension and right heart failure in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice","volume":"110","author":"Otto","year":"2004","journal-title":"Circulation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1161\/hc0302.102610","article-title":"Morphological predictors of arterial remodeling in coronary atherosclerosis","volume":"105","author":"Burke","year":"2002","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/CRD.0b013e31829dea90","article-title":"Pathophysiology of coronary vascular remodeling: Relationship with traditional risk factors for coronary artery disease","volume":"22","author":"Pant","year":"2014","journal-title":"Cardiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1161\/CIRCULATIONAHA.119.044720","article-title":"Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction","volume":"141","author":"Williams","year":"2020","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1016\/j.jacc.2020.10.021","article-title":"Impact of Plaque Burden Versus Stenosis on Ischemic Events in Patients with Coronary Atherosclerosis","volume":"76","author":"Mortensen","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1046\/j.1460-9568.2000.00118.x","article-title":"Pituitary adenylate cyclase-activating polypeptide promotes the survival of basal forebrain cholinergic neurons in vitro and in vivo: Comparison with effects of nerve growth factor","volume":"12","author":"Takei","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Reglodi, D., Tamas, A., Bosnyak, I., Atlasz, T., Szabo, E., Li, L., Horvath, G., Opper, B., Kiss, P., and Lucas, L. (2025). Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199650"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Xiong, Z., Zhou, X., Li, Y., and Yang, L. (2025). PACAP inhibits sepsis-associated acute lung injury by inhibiting the Sp1\/AQP1 pathway. Peptides, 191.","DOI":"10.1016\/j.peptides.2025.171411"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107573","DOI":"10.1016\/j.psyneuen.2025.107573","article-title":"PACAP mitigates traumatic brain injury progression via ELF3\/ZO-1 axis-mediated blood-brain barrier repair","volume":"180","author":"Bai","year":"2025","journal-title":"Psychoneuroendocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1161\/CIRCRESAHA.108.187302","article-title":"Lipid incorporation inhibits Src-dependent assembly of fibronectin and type I collagen by vascular smooth muscle cells","volume":"104","author":"Frontini","year":"2009","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13531","DOI":"10.1073\/pnas.1735526100","article-title":"Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading","volume":"100","author":"Rong","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0021-9150(97)00136-6","article-title":"Subendothelial smooth muscle cells of human aorta express macrophage antigen in situ and in vitro","volume":"135","author":"Andreeva","year":"1997","journal-title":"Atherosclerosis"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.4049\/jimmunol.1800122","article-title":"Vasoactive Intestinal Peptide Ameliorates Acute Myocarditis and Atherosclerosis by Regulating Inflammatory and Autoimmune Responses","volume":"200","author":"Benitez","year":"2018","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.peptides.2007.06.021","article-title":"Maxadilan, a PAC1 receptor agonist from sand flies","volume":"28","author":"Lerner","year":"2007","journal-title":"Peptides"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1749-6632.1998.tb11185.x","article-title":"Maxadilan is a specific agonist and its deleted peptide (M65) is a specific antagonist for PACAP type 1 receptor","volume":"865","author":"Uchida","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.yexcr.2019.01.011","article-title":"Migration versus proliferation as contributor to in vitro wound healing of vascular endothelial and smooth muscle cells","volume":"376","author":"Ammann","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jang, S., Jeong, J.-Y., and Huh, W.-K. (2026). Activation of the pituitary adenylate cyclase-activating polypeptide type I receptor promotes neuroblastoma proliferation and migration through distinct G protein pathways. Cell Commun. Signal., 24.","DOI":"10.1186\/s12964-026-02660-2"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/362801a0","article-title":"The pathogenesis of atherosclerosis: A perspective for the 1990s","volume":"362","author":"Ross","year":"1993","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1161\/CIRCRESAHA.108.186064","article-title":"Oxidized phospholipids induce type VIII collagen expression and vascular smooth muscle cell migration","volume":"104","author":"Cherepanova","year":"2009","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1161\/CIRCRESAHA.107.152736","article-title":"Oxidized phospholipids induce phenotypic switching of vascular smooth muscle cells in vivo and in vitro","volume":"101","author":"Pidkovka","year":"2007","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3892\/ijmm.2014.1681","article-title":"Oxidized low-density lipoprotein increases the proliferation and migration of human coronary artery smooth muscle cells through the upregulation of osteopontin","volume":"33","author":"Liu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/S0022-2275(20)37921-9","article-title":"Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid","volume":"24","author":"Morel","year":"1983","journal-title":"J. Lipid Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1161\/01.ATV.17.10.2225","article-title":"DNA fragmentation and ultrastructural changes of degenerating cells in atherosclerotic lesions and smooth muscle cells exposed to oxidized LDL in vitro","volume":"17","author":"Jovinge","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1161\/01.ATV.16.3.416","article-title":"Contrary effects of lightly and strongly oxidized LDL with potent promotion of growth versus apoptosis on arterial smooth muscle cells, macrophages, and fibroblasts","volume":"16","year":"1996","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1161\/01.ATV.21.6.955","article-title":"Oxidized LDL modulates Bax\/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells","volume":"21","author":"Kataoka","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1161\/01.CIR.102.22.2680","article-title":"Oxidized low-density lipoprotein is associated with apoptosis of vascular smooth muscle cells in human atherosclerotic plaques","volume":"102","author":"Okura","year":"2000","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1083\/jcb.130.1.193","article-title":"Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: Spatial and temporal modulation of PDGF chemotactic signal transduction","volume":"130","author":"Bornfeldt","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0898-6568(99)00020-0","article-title":"Crosstalk between protein kinase A and growth factor receptor signaling pathways in arterial smooth muscle","volume":"11","author":"Bornfeldt","year":"1999","journal-title":"Cell Signal."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1152\/physrev.00030.2008","article-title":"Mitochondrial dynamics in mammalian health and disease","volume":"89","author":"Liesa","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.cmet.2013.03.002","article-title":"Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure","volume":"17","author":"Liesa","year":"2013","journal-title":"Cell Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bbamcr.2012.06.025","article-title":"Proteolytic control of mitochondrial function and morphogenesis","volume":"1833","author":"Anand","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1006\/exnr.2000.7333","article-title":"Abnormal Mitochondrial Morphology in Sporadic Parkinson\u2019s and Alzheimer\u2019s Disease Cybrid Cell Lines","volume":"162","author":"Trimmer","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gao, J., Wang, L., Liu, J., Xie, F., Su, B., and Wang, X. (2017). Abnormalities of Mitochondrial Dynamics in Neurodegenerative Diseases. Antioxidants, 6.","DOI":"10.3390\/antiox6020025"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.biocel.2009.05.004","article-title":"Dynamic organization of mitochondria in human heart and in myocardial disease","volume":"41","author":"Hoppel","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.cell.2006.06.010","article-title":"Mitochondria: Dynamic organelles in disease, aging, and development","volume":"125","author":"Chan","year":"2006","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.devcel.2007.02.002","article-title":"Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster","volume":"12","author":"Goyal","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1002\/jor.24828","article-title":"Drp1-mediated mitochondrial fission is involved in oxidized low-density lipoprotein-induced AF cella poptosis","volume":"39","author":"Wu","year":"2021","journal-title":"J. Orthop. Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Liu, S., Zhao, Y., Yao, H., Zhang, L., Chen, C., Zheng, Z., and Jin, S. (2023). DRP1 knockdown and atorvastatin alleviate ox-LDL-induced vascular endothelial cells injury: DRP1 is a potential target for preventing atherosclerosis. Exp. Cell Res., 429.","DOI":"10.1016\/j.yexcr.2023.113688"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/90976","article-title":"Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA","volume":"7","author":"Nakada","year":"2001","journal-title":"Nat. Med."},{"key":"ref_91","first-page":"2699","article-title":"Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles","volume":"14","author":"Yoneda","year":"1994","journal-title":"Mol. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.redox.2014.11.006","article-title":"Mitochondrial dynamics and mitochondrial quality control","volume":"4","author":"Ni","year":"2015","journal-title":"Redox Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"E2967","DOI":"10.1073\/pnas.1303872110","article-title":"Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion","volume":"110","author":"Rolland","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/12\/1127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:44:36Z","timestamp":1782535476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/12\/1127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":93,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cells15121127"],"URL":"https:\/\/doi.org\/10.3390\/cells15121127","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}