期刊
BASIC RESEARCH IN CARDIOLOGY
卷 112, 期 3, 页码 -出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-017-0613-6
关键词
Caveolar proteins; Cardiac compliance; Reactive hyperaemia; Ischaemia-reperfusion; Nitric oxide synthase; Membrane permeability; Stretch-response
资金
- National Health and Medical Research Council of Australia [APP1037320, APP1058565, APP569542, APP1085996]
- Academy of Finland [Decision 266263]
Caveolae and associated cavin and caveolins may govern myocardial function, together with responses to mechanical and ischaemic stresses. Abnormalities in these proteins are also implicated in different cardiovascular disorders. However, specific roles of the cavin-1 protein in cardiac and coronary responses to mechanical/metabolic perturbation remain unclear. We characterised cardiovascular impacts of cavin-1 deficiency, comparing myocardial and coronary phenotypes and responses to stretch and ischaemia-reperfusion in hearts from cavin-1(+/+) and cavin-1(-/-) mice. Caveolae and caveolins 1 and 3 were depleted in cavin-1(-/-) hearts. Cardiac ejection properties in situ were modestly reduced in cavin-1(-/-) mice. While peak contractile performance in ex vivo myocardium from cavin-1(-/-) and cavin-1(+/+) mice was comparable, intrinsic beating rate, diastolic stiffness and Frank-Starling behaviour (stretch-dependent diastolic and systolic forces) were exaggerated in cavin-1(-/-) hearts. Increases in stretch-dependent forces were countered by NOS inhibition (100 mu M L-NAME), which exposed negative inotropy in cavin-1(-/-) hearts, and were mimicked by 100 mu M nitroprusside. In contrast, chronotropic differences appeared largely NOS-independent. Cavin-1 deletion also induced NOS-dependent coronary dilatation, >= 3-fold prolongation of reactive hyperaemic responses, and exaggerated pressure-dependence of coronary flow. Stretch-dependent efflux of lactate dehydrogenase and cardiac troponin I was increased and induction of brain natriuretic peptide and c-Fos inhibited in cavin-1(-/-) hearts, while ERK1/2 phospho-activation was preserved. Post-ischaemic dysfunction and damage was also exaggerated in cavin-1(-/-) hearts. Diverse effects of cavin-1 deletion reveal important roles in both NOS-dependent and -independent control of cardiac and coronary functions, together with governing sarcolemmal fragility and myocardial responses to stretch and ischaemia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据