1 Introduction
CD36 is a member of the class B2 scavenger receptor family, including low density lipoprotein (LDL), high density lipoprotein (HDL)-bound scavenger receptor B1, and HDL-bound scavenger receptor scavenger receptor B3(Luiken et al., 2016). The ligands of CD36 are mainly divided into lipid ligands and protein ligands. The former includes oxidized LDL particles(Jay et al., 2015), long-chain fatty acids (LCFA)(Liu et al., 2018a), phospholipids(Lee et al., 2015), etc., and the latter includes collagen(Lee et al., 2019), thrombospondin(Simantov et al., 2005). In addition, apoptotic cells also serve as ligands for CD36(Albert et al., 1998).
CD36 is expressed in various tissues, including endothelial cells(Son et al., 2018), cardiac muscle cells(Yu et al., 2020), renal tubular epithelial cells(Hou et al., 2015), liver cells(Couturier et al., 2019), adipocytes(Ladanyi et al., 2018), platelets(Yang et al., 2018), macrophage(Frank et al., 2019), et al., and involved in many pathophysiological processes, including immune regulation(Wang and Li, 2019), metabolic regulation(Glatz and Luiken, 2017) et al. In myocardial tissue, CD36 mainly mediates the uptake of long-chain fatty acids(Kim and Dyck, 2016). Fatty acids provide over 70% of the ATP for myocardial tissue and most of the fatty acids enter the cells through protein-mediated diffusion. Importantly, 70% of total fatty acid intake is mediated by CD36(Kim and Dyck, 2016). Therefore, CD36 is indispensable in cardiovascular system.
The synthesis and translocation of CD36 are affected by many stimuli. Short-term stimulation of insulin promotes the translocation of CD36 from the endosome to the cell membrane(Luiken et al., 2002), while long-term stimulation induces its protein synthesis(Cheng et al., 2011). Hyperglycemia and hyperlipidemia also facilitate the translocation of CD36 to the cell membrane(Angin et al., 2012). It has been proved that impaired synthesis and abnormal distribution of CD36 shorten myocardial energy supply(Sung et al., 2017), resulting in the impairment of myocardial contractile function(Abumrad and Goldberg, 2016). Pressure overload decreases a controller of CD36 synthesis, nuclear receptor peroxisome proliferator-activated receptor α (PPARα)(Dobrzyn et al., 2013), resulting in insufficient myocardial fatty acid uptake and the accumulation of toxic lipids, and ultimately leading to heart failure. However, down-regulating CD36 in diabetic cardiomyopathy reduces the toxic lipids(Xu et al., 2019), and improves the contractile function of the heart. Therefore, the influence of CD36 on myocardium may not be consistent and largely depend on the pathological background.
In this review, we summarize regulation and post translational modification of CD36, and focus on its role in the cardiovascular diseases, especially in ischemia/reperfusion, diabetic cardiomyopathy, pathological cardiac hypertrophy, and physiological cardiac hypertrophy. we also provide some suggestions for basic and clinical research of CD36, aiming to emphasize the significance of CD36 in the cardiovascular system and shed light on its therapeutic target.