Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice.
The role of angiotensin II (Ang II) in promoting cardiac hypertrophy is well known; however, its role in a spontaneous model of hypertrophy in mice lacking the protein caveolin-1 (Cav-1 KO) has not been explored. In this study, WT and Cav-1 KO mice were treated with angiotensin receptor blocker (ARB), telmisartan (Telm), and cardiac function was assessed by echocardiography. Treatment of Cav-1 KO mice with Telm significantly improved cardiac function compared with age-matched vehicle-treated Cav-1 KO mice, whereas Telm did not affect cardiac function in WT mice. Both left ventricular (LV) weight to body weight ratios and LV to tibial length ratios were also reverted by Telm in Cav-1 KO but not in WT mice. LV hypertrophy was associated with increased expression of natriuretic peptides A and B, β-myosin heavy chain and TGF-β, and Telm treatment normalized the expression of these genes. Telm reduced the expression of collagen genes (Col1A and Col3A) and associated perivascular fibrosis in intramyocardial vessels in Cav-1 KO mice. In conclusion, Telm treatment reduces indexes of cardiac hypertrophy in this unique genetic model of spontaneous LV hypertrophy.
Krieger
Marta H
MH
Department of Anatomy, Cell Biology, Physiology and Biophysics, Institute of Biology, State University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Di Lorenzo
Annarita
A
Teutsch
Christine
C
Kauser
Katalin
K
Sessa
William C
WC
D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D051242:Caveolin 1 / Q000172:deficiency*; D005786:Gene Expression Regulation / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D051242:Caveolin 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000077333:Telmisartan