CD36 knockdown attenuates pressure overload-induced cardiac injury by preventing lipotoxicity and improving myocardial energy metabolism

In this study, we reported that CD36 CKD, not CD36 CKO, was able to protect against cardiac functional impairment in the pressure-overload heart. Manipulating CD36 was a feasible strategy to achieve an optimal point which maintain cardiac energy supply while avoiding lipotoxicity.

Cardiac-specific CD36 totally knockout (CKO) and partially knockdown (CKD) mice were induced by genetics deletion and AAV-9 CD36 shRNA injection, respectively. Both CD36 CKO and CKD mice were subjected to transverse aortic constriction (TAC) operation to induce cardiac pressure overload. Cardiac function was measured by echocardiography. Cardiac lipid accumulation, FA oxidation and metabolic sate were also examined.

This study aims to investigate the feasibility of CD36 partially knockdown in the prevention of cardiac lipotoxicity and functional impairment in pressure overload heart.

TAC operation induced significant cardiac dysfunction and pathological cardiac remodeling, accompanied by aberrant intra-myocardial lipid deposition and impaired FAO capacity. CD36 CKO attenuated aberrant lipid accumulation in the failing heart, while aggravated TAC-induced cardiac energy deprivation and oxidative stress. In contrast, CD36 CKD ameliorated TAC-induced lipid accumulation and excessive oxidative stress in the mice heart, accompanied by improved mitochondrial respiration function. Moreover, CD36 CKD induced a robust increase in glycolytic flux into the TCA cycle, which led to preserved ATP generation. As a result, CD36 CKD prevented the development of pressure overload-induced cardiac hypertrophy and dysfunction.