Key result
Depletion of CD8+ T cells in a murine model of pressure overload-induced heart failure promoted early cardioprotective hypertrophy and suppressed late-stage heart failure by driving the differentiation of cardioprotective macrophages.
Why the study?
Heart-resident and infiltrated macrophages play important roles in cardiac remodeling during pressure overload, but the possible roles of T cells in this process were not well characterized.
Does CD8+ T cell depletion prevent heart failure progression in a murine model of pressure overload?
Does CD8+ T cell depletion prevent heart failure progression in a murine model of pressure overload?
CD8+ T cell depletion in a murine model of pressure overload induces early cardioprotective hypertrophy and prevents late-stage heart failure by modulating macrophage phenotypes.
Should not change heart failure practice; hypothesis-generating for CD8+ T-cell modulation in pressure overload.
Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. Heart-resident and infiltrated macrophages have been shown to play important roles in the cardiac remodeling that occurs in response to cardiac pressure overload. However, the possible roles of T cells in this process, have not been well characterized. Here we show that T cell depletion conferred late-stage heart protection but induced cardioprotective hypertrophy at an early stage of heart failure caused by cardiac pressure overload. Single-cell RNA sequencing analysis revealed that CD8 + T cell depletion induced cardioprotective hypertrophy characterized with the expression of mitochondrial genes and growth factor receptor genes. CD8 + T cells regulated the conversion of both cardiac-resident macrophages and infiltrated macrophages into cardioprotective macrophages expressing growth factor genes such as Areg , Osm , and Igf1 , which have been shown to be essential for the myocardial adaptive response after cardiac pressure overload. Our results demonstrate a dynamic interplay between cardiac CD8 + T cells and macrophages that is necessary for adaptation to cardiac stress, highlighting the homeostatic functions of resident and infiltrated macrophages in the heart.
No takes yet. Share an insight, caveat, or question.
Komai et al. (2021) studied Heart failure (pressure overload-induced cardiac hypertrophy). CD8+ T cell depletion vs. Wild-type mice or vehicle (PBS) was evaluated on Cardiac hypertrophy and heart failure progression (LVEF, LVDd, LVPWd). Depletion of CD8+ T cells in a murine model of pressure overload-induced heart failure promoted early cardioprotective hypertrophy and suppressed late-stage heart failure by driving the differentiation of cardioprotective macrophages.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: