{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:04:35Z","timestamp":1791489875578,"version":"4.3.4"},"reference-count":38,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HE 1587\/12-2"],"award-info":[{"award-number":["HE 1587\/12-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have characterised the functional properties of lipoma-preferred partner (LPP), a Lin11\u2013Isl1\u2013Mec3 (LIM)-domain protein, which is most closely related to the mechanotransducer zyxin but selectively expressed by smooth muscle cells, including VSMCs in adult mice. VSMCs isolated from the aorta of LPP knockout (LPP-KO) mice displayed a higher rate of proliferation than their wildtype (WT) counterparts, and when cultured as three-dimensional spheroids, they revealed a higher expression of the proliferation marker Ki 67 and showed greater invasion into a collagen gel. Accordingly, the gelatinase activity was increased in LPP-KO but not WT spheroids. The LPP-KO spheroids adhering to the collagen gel responded with decreased contraction to potassium chloride. The relaxation response to caffeine and norepinephrine was also smaller in the LPP-KO spheroids than in their WT counterparts. The overexpression of zyxin in LPP-KO VSMCs resulted in a reversal to a more quiescent differentiated phenotype. In native VSMCs, i.e., in isolated perfused segments of the mesenteric artery (MA), the contractile responses of LPP-KO segments to potassium chloride, phenylephrine or endothelin-1 did not vary from those in isolated perfused WT segments. In contrast, the myogenic response of LPP-KO MA segments was significantly attenuated while zyxin-deficient MA segments displayed a normal myogenic response. We propose that LPP, which we found to be expressed solely in the medial layer of different arteries from adult mice, may play an important role in controlling the quiescent contractile phenotype of VSMCs.<\/jats:p>","DOI":"10.3390\/cells12182315","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T23:17:20Z","timestamp":1695165440000},"page":"2315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Alexandra","family":"Sporkova","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taslima","family":"Nahar","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhajit","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Sens-Albert","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prisca Amayi Patricia","family":"Friede","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaafar","family":"Al-Hasani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7010-3684","authenticated-orcid":false,"given":"Markus","family":"Hecker","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.00041.2003","article-title":"Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease","volume":"84","author":"Owens","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1073\/pnas.87.12.4600","article-title":"Cell proliferation in human coronary arteries","volume":"87","author":"Gordon","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/jcp.25208","article-title":"Smooth Muscle Cell Differentiation: Model Systems, Regulatory Mechanisms, and Vascular Diseases","volume":"231","author":"Shi","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jvssci.2021.04.001","article-title":"Targeting smooth muscle cell phenotypic switching in vascular disease","volume":"2","author":"Chakraborty","year":"2021","journal-title":"JVS Vasc. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrm2593","article-title":"Environmental sensing through focal adhesions","volume":"10","author":"Geiger","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.devcel.2020.09.022","article-title":"Mechanosensing through Direct Binding of Tensed F-Actin by LIM Domains","volume":"55","author":"Sun","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25532","DOI":"10.1073\/pnas.2004656117","article-title":"Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism","volume":"117","author":"Winkelman","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/CIRCRESAHA.110.227850","article-title":"Zyxin Mediation of Stretch-Induced Gene Expression in Human Endothelial Cells","volume":"107","author":"Babu","year":"2010","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1161\/01.HYP.0000119189.82659.52","article-title":"Focal Adhesion Protein Zyxin Is a Mechanosensitive Modulator of Gene Expression in Vascular Smooth Muscle Cells","volume":"43","author":"Cattaruzza","year":"2004","journal-title":"Hypertension"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3389\/fphys.2012.00472","article-title":"Zyxin is involved in regulation of mechanotransduction in arteriole smooth muscle cells","volume":"3","author":"Sun","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1091\/mbc.11.1.117","article-title":"LPP, an Actin Cytoskeleton Protein Related to Zyxin, Harbors a Nuclear Export Signal and Transcriptional Activation Capacity","volume":"11","author":"Petit","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"C674","DOI":"10.1152\/ajpcell.00608.2002","article-title":"LPP, a LIM protein highly expressed in smooth muscle","volume":"285","author":"Gorenne","year":"2003","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/01.RES.0000261351.54147.de","article-title":"Angiotensin II, Focal Adhesion Kinase, and PRX1 Enhance Smooth Muscle Expression of Lipoma Preferred Partner and its Newly Identified Binding Partner Palladin to Promote Cell Migration","volume":"100","author":"Jin","year":"2007","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e001712","DOI":"10.1161\/JAHA.114.001712","article-title":"Loss of the Mechanotransducer Zyxin Promotes a Synthetic Phenotype of Vascular Smooth Muscle Cells","volume":"4","author":"Ghosh","year":"2015","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1083\/jcb.143.5.1341","article-title":"Integration of Endothelial Cells in Multicellular Spheroids Prevents Apoptosis and Induces Differentiation","volume":"143","author":"Korff","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Garg, J., Sporkova, A., Hecker, M., and Korff, T. (2022). Tracing G-Protein-Mediated Contraction and Relaxation in Vascular Smooth Muscle Cell Spheroids. Cells, 12.","DOI":"10.3390\/cells12010128"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1161\/01.RES.75.1.41","article-title":"Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation","volume":"75","author":"Pauly","year":"1994","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0303-7207(81)90112-X","article-title":"Phosphodiesterase inhibitors as tools in cyclic nucleotide research: A precautionary comment","volume":"23","author":"Wells","year":"1981","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"L334","DOI":"10.1152\/ajplung.00103.2012","article-title":"Caffeine relaxes smooth muscle through actin depolymerization","volume":"303","author":"Tazzeo","year":"2012","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/BF00169741","article-title":"Direct inhibition of chicken gizzard smooth muscle contractile apparatus by caffeine","volume":"341","author":"Ozaki","year":"1990","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"180160","DOI":"10.1038\/sdata.2018.160","article-title":"Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types","volume":"5","author":"He","year":"2018","journal-title":"Sci. Data"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nature25739","article-title":"A molecular atlas of cell types and zonation in the brain vasculature","volume":"554","author":"Vanlandewijck","year":"2018","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00018-022-04133-4","article-title":"Zyxin protects from hypertension-induced cardiac dysfunction","volume":"79","author":"Ghosh","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5400","DOI":"10.1073\/pnas.0808793106","article-title":"Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound","volume":"106","author":"Kiyonaka","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1074\/jbc.M206106200","article-title":"The Focal Adhesion and Nuclear Targeting Capacity of the LIM-containing Lipoma-preferred Partner (LPP) Protein","volume":"278","author":"Petit","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1165\/rcmb.2002-0206OC","article-title":"The RhoA\/Rho Kinase Pathway Regulates Nuclear Localization of Serum Response Factor","volume":"29","author":"Liu","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1128\/MCB.25.8.3173-3181.2005","article-title":"Muscle-Specific Signaling Mechanism That Links Actin Dynamics to Serum Response Factor","volume":"25","author":"Kuwahara","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1074\/jbc.M005505200","article-title":"Smooth Muscle Differentiation Marker Gene Expression Is Regulated by RhoA-mediated Actin Polymerization","volume":"276","author":"Mack","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1006\/dbio.2001.0403","article-title":"Coronary Smooth Muscle Differentiation from Proepicardial Cells Requires RhoA-Mediated Actin Reorganization and p160 Rho-Kinase Activity","volume":"240","author":"Lu","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3389\/fphys.2015.00335","article-title":"\u201cSmooth Muscle Cell Stiffness Syndrome\u201d\u2014Revisiting the Structural Basis of Arterial Stiffness","volume":"6","author":"Sehgel","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H380","DOI":"10.1152\/ajpheart.2002.282.1.H380","article-title":"Effects of age, gender, and blood pressure on myogenic responses of mesenteric arteries from C57BL\/6 mice","volume":"282","author":"Gros","year":"2002","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101813","DOI":"10.1016\/j.arr.2022.101813","article-title":"Arterial myogenic response and aging","volume":"84","author":"Cui","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/bs.apha.2017.08.002","article-title":"Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease","volume":"81","author":"Wang","year":"2018","journal-title":"Adv. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.jvs.2004.08.035","article-title":"Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction","volume":"40","author":"Chew","year":"2004","journal-title":"J. Vasc. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.jss.2008.09.022","article-title":"MMP-2 Induced Vein Relaxation via Inhibition of [Ca2+]e-Dependent Mechanisms of Venous Smooth Muscle Contraction. Role of RGD Peptides","volume":"159","author":"Raffetto","year":"2010","journal-title":"J. Surg. Res."},{"key":"ref_36","first-page":"1497","article-title":"Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension","volume":"595","author":"Cidad","year":"2016","journal-title":"J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s00424-005-1460-0","article-title":"The diacylgylcerol-sensitive TRPC3\/6\/7 subfamily of cation channels: Functional characterization and physiological relevance","volume":"451","author":"Dietrich","year":"2005","journal-title":"Pfl\u00fcgers Arch.-Eur. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s12079-017-0415-5","article-title":"Emerging roles for LPP in metastatic cancer progression","volume":"12","author":"Ngan","year":"2018","journal-title":"J. Cell. Commun. Signal."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2315\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:59Z","timestamp":1760129639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":38,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182315"],"URL":"https:\/\/doi.org\/10.3390\/cells12182315","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]}}}