The Inflammatory and Fibrotic Response in the Murine Pressure‐overloaded Heart

Abstract

Cardiac pressure overload results in hypertrophy and fibrotic remodeling of the ventricle. We hypothesized that development of fibrosis in the pressure‐overloaded heart may be preceded by activation an inflammatory cascade; subsequent induction of inhibitory pathways (such as TGF‐β) may suppress inflammation while inducing fibrosis. C57/BL6 mice underwent transverse aortic constriction (TAC) protocols. Chemokine (MCP‐1, MIP‐1alpha, RANTES and Lymphotactin) and pro‐inflammatory cytokine (TNF‐alpha and IL‐1beta) expression was induced in the pressure overloaded heart after 3–7 days of TAC. Upregulation of inflammatory mediators was associated with perivascular and interstitial macrophage infiltration. Induction of pro‐inflammatory mediators was followed by a late upregulation of TGF‐β isoforms associated with expression of the matricellular proteins tenascin‐C, OPN and TSP‐1. Inflammatory activity decreased after 28 days of TAC; at this timepoint established fibrosis was noted. The development of fibrosis was associated with cardiac hypertrophy, ventricular dilation and systolic dysfunction. In the pressure overloaded heart, late induction of inhibitory mediators, such as TGF‐β, may suppress inflammation while inducing fibrosis. Experiments using genetically targeted animals will dissect the mechanisms responsible for fibrotic remodeling of the ventricle (R01 HL‐76246).

L-carnitine attenuated hyperuricemia-associated left ventricular remodeling through ameliorating cardiomyocytic lipid deposition

“…Through LVR, the heart may temporarily preserve cardiac output, but progressive LVR is maladaptive and leads to HF (Pezel et al, 2021). The initial stage of LVR manifests as marked hypertrophy without ventricular enlargement or systolic functional impairment, followed by the development of chamber dilation and systolic dysfunction (Xia et al, 2009). The available studies have generally considered cardiomyocyte physiological activity with insufficient energy to be one of the mechanisms contributing to LVR development (Dalal and Mishra, 2017;Tuomainen and Tavi, 2017).…”