Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-β mediated fibrosis

The effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.We postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.Hypertensive heart disease describes a phase of remodeling which occurs in the myocardium when exposed to sustained elevation in arterial blood pressure or hypertrophic substances associated with the hypertension syndrome. The two most notable features of hypertensive heart disease are myocyte hypertrophy and reactive fibrosis. The relationship between reactive fibrosis and hypertension is well described [1-3].In physiological terms, the effect of this fibrosis is a reduction in compliance of the myocardium and diastolic dysfunction. This premise is based on two principles. Firstly, the addition of fibrillar collagen to normal tissue results in reduced compliance of that tissue, and secondly, regression of such fibrosis improves compliance and reduces cardiac stiffness [4-8]. The synthesis and degradation of fibrillar collagen is regulated by the myocardial fibroblast. Fibroblast differentiation to the more active myofibroblast form is a hallmark of cardiac fibrosis, and is associated with increased collagen production, enhanced proliferative and migratory potential, and is associated with increased expression of alpha-smooth muscle actin (AS