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.