Alexandra M Garvin, Dana B Floyd, Alexis C Bailey, Merry L Lindsey, Chad C Carroll, Taben M Hale
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引用次数: 0
Abstract
Hypertension increases the prevalence of heart failure to a greater extent in women than in men. The fibrotic remodeling of the left ventricle is a major contributor to increased myocardial stiffness and eventual decrease in cardiac function. Injury-induced cardiac fibrosis can be prevented in the spontaneously hypertensive rat (SHR) by transient angiotensin converting enzyme inhibition (ACEi) in males. Whether transient ACEi also protects against fibrosis in females is not known. In the present study, we evaluated angiotensin II (Ang II)-induced cardiac fibrosis and related signaling in male and female SHR to determine how these responses are altered by prior transient ACEi treatment. Relative changes in blood pressure response to both ACEi and Ang II were similar between sexes, while Ang II-induced cardiac hypertrophy was attenuated by prior ACEi in males only. Ang II-induced changes in gene expression for collagens I, III, and IV were attenuated by prior ACEi in males, but not females. Despite these sex-specific differences, prior ACEi attenuated Ang II-induced increases in fibrogenic proteins (phosphorylated SMAD3/SMAD3, periostin, and lysyl oxidase) and pro-oxidative proteins (NOX2 and NOX4), as well as hydroxyproline content similarly in both sexes. Interestingly, a positive correlation between angiotensin II type 1 receptor gene expression and Col1a1 in Ang II treated males is absent in the female SHRs. The observed sex differences in the protection afforded by prior ACEi suggest altered signaling for collagen deposition that may lead to a greater understanding of the sex-dependent efficacy of antihypertensive drugs.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.