Cited by 102Renin-Angiotensin System StudiesCardiac Fibrosis and RemodelingAdipokines, Inflammation, and Metabolic Diseases

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An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1

Rajapurohitam, Venkatesh, Javadov, Sabzali, Purdham, Daniel M., Kirshenbaum, Lorrie A., Karmazyn, Morris·2006·Journal of Molecular and Cellular Cardiology

DOI 10.1016/j.yjmcc.2006.05.001

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Abstract

Leptin is a 16 kDa product of the obesity gene secreted primarily by adipocytes. We recently identified cardiomyocytes as a target for the direct hypertrophic effects of leptin and suggested that leptin may be a biological link between obesity and cardiovascular pathologies. Activation of the renin-angiotensin and endothelin systems is associated with development of cardiovascular diseases and plasma renin levels are elevated in obese individuals. We therefore determined possible interaction between these factors in mediating hypertrophy in cultured neonatal rat ventricular myocytes. Treatment for 24 h with leptin (3.1 nM), angiotensin II (100 nM) or endothelin-1 (ET-1, 10 nM) significantly increased cell area by 37%, 36% and 35%, respectively and significantly increased gene expression of myosin light chain-2 and alpha-skeletal actin as well as leucine incorporation. The hypertrophic effects of all three agents were prevented by leptin and a leptin triple mutant receptor antagonist whereas the AT(1) receptor blocker (Sar1-lle(8))-Ang II or the ET(A) receptor blocker BQ123 was ineffective against leptin-induced hypertrophy. Both angiotensin II and ET-1 significantly increased leptin levels in the culture medium by fivefold. Moreover, both angiotensin II and ET-1 increased the gene expression of the short form (OBRa) by 180% and long form (OBRb) of leptin receptors by 200%, and this increase was abolished by both leptin receptor and leptin antibodies and leptin triple mutant. Although both angiotensin II and ET-1 increased phosphorylation of MAPK (p38, ERK1/2 and JNK) and NF-kappaB, the ability of leptin blockade to attenuate the hypertrophic responses was generally dissociated from these effects suggesting an alternate, yet to be identified cellular pathway mediating this role of leptin. Our studies therefore suggest a novel autocrine function for leptin in mediating the hypertrophic effects of both angiotensin II and ET-1 in cardiac myocytes.

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Authors: Rajapurohitam, V., Javadov, S., Purdham, D. M., Kirshenbaum, L. A., & Karmazyn, M.
Affiliations: Western University (CA)
St. Boniface Hospital (CA)
ORCID: Javadov, Sabzali
Kirshenbaum, Lorrie A.
Karmazyn, Morris
Venue: Journal of Molecular and Cellular Cardiology
Publisher: Elsevier BV
Published: 2006-08
Volume: 41
Issue: 2
Pages: 265-274
ISSN: 0022-2828 (ISSN-L)
DOI: 10.1016/j.yjmcc.2006.05.001
OpenAlex: W2008347790
Cited by: 102
References: 43
Citations by year: 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 8 · 2012: 7
FWCI: 5.69
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Molecular and Cellular Cardiology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: leptin, cardiomyocyte hypertrophy, angiotensin II, endothelin-1, autocrine signaling, leptin receptor, obesity, renin-angiotensin system, endothelin system, MAPK signaling, NF-κB, myosin light chain 2, alpha-skeletal actin, ventricular myocytes
MeSH terms: Angiotensin II, Animals, Animals, Newborn, Cells, Cultured, Gene Expression Regulation, Cardiomegaly, Heart Ventricles, Obesity, Vasoconstrictor Agents, Rats, Sprague-Dawley, Adipocytes, Endothelin-1, Autocrine Communication, Leptin, MAP Kinase Signaling System, Myocytes, Cardiac, Rats

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An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1

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