Premium
Mechanical stretch‐induced hypertrophy of neonatal rat ventricular myocytes is mediated by β 1 ‐integrin‐microtubule signaling pathways
Author(s) -
Yutao Xi,
Geru Wu,
Xiaojun Bai,
Tao Geng,
Aiqun Ma
Publication year - 2006
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2005.05.014
Subject(s) - integrin , atrial natriuretic peptide , medicine , colchicine , endocrinology , myocyte , chemistry , receptor , microbiology and biotechnology , biology
Background: Mechanical stress plays a crucial role in tissue morphogenesis and remodeling. These processes depend in part on force transmission mediated through integrins and the cytoskeleton. Methods: Ventricular myocytes isolated from neonatal Sprague–Dawley rats (NRVMs) were exposed to persistent centrifugal force stretch for 12 or 24 h. The NRVMs were exposed to colchicine (4 μmol/ml) and anti‐integrin β 1 specific antibody (10 μg/ml). Cell viability was assessed by MTT assay and lactate dehydrogenase (LDH) activity. Incorporation of 3 H‐leucine, and atrial natriuretic peptide (ANP) and angiotensin II (Ang II) levels were assessed. Pixel intensity and distribution of the microtubule were estimated from laser scanning confocal images. Results: Changes in LDH release and the MTT assay showed that 180 rpm. centrifugal force had minimal effect on the viability and number of NRVMs. Mechanical stretch significantly increased 3 H‐leucine incorporation into cardiomyocytes. Anti‐integrin β 1 blocking antibody effectively inhibited the increase in 3 H‐leucine incorporation and release of ANP ( p <0.05). Following anti‐integrin‐β 1 ‐blocking antibody, the pixel intensity of the microtubule image was decreased after both12 and 24 h stretch, this was similar to the effect of colchicine. Both treatments also inhibited the secretion of Ang II induced by stretch ( p <0.05). Conclusions: Anti‐integrin‐β 1 ‐blocking antibody and colchicine had similar effects, partly inhibiting the stretch‐induced increase in microtubule polymerization and the secretion of Ang II in hypertrophic cardiac myocytes.