Sterol carrier protein 2: A promising target in the pathogenesis of atherosclerosis

Abstract

Atherosclerosis, the underlying pathophysiological basis of cardiovascular disease, has been recognized as a lipid-driven chronic inflammatory disease. Sterol carrier protein 2 (SCP-2) is a 13-kDa non-specific lipid-transfer protein expressed by various tissues and cells, such as liver, heart, vascular smooth muscle cells (VSMCs), and macrophages. SCP-2 has an extensive role in cardiovascular and metabolic diseases. Recently, SCP-2 was reported to promote the development of atherosclerosis by regulating lipid metabolism and peroxidation, endocannabinoid metabolism, vascular inflammation, and fatty acid metabolism. In this review, we summarized the recent advances regarding the role of SCP-2 in the pathogenesis of atherosclerosis and tried to provide a rationale for future investigation and a better understanding of the biological functions of SCP-2 in atherosclerotic cardiovascular disease.

Keywords: Atherosclerosis; Fatty acid metabolism; Lipid metabolism; SCP-2; Vascular inflammation.

Figure 1

SCP-2-mediated regulation and the major cardiometabolic risk factors of atherosclerosis. Abbreviations: ACAT1, acyl-CoA: cholesterol acyltransferase 1; SR-A, scavenger receptor class A; ABCA/G1, ATP binding cassette transporter A/G1; NPC1L1, Niemann-Pick C1-like 1; TICE, transintestinal cholesterol efflux; LDLR, low-density lipoprotein receptor; PLOOH, phospholipid hydroperoxide; AEA, N-arachidonoylethanolamine; ChOOH, Cholesterol hydroperoxide; 2-AG, 2-arachinoylglicerol; CB1/2, cannabinoid receptor 1/2; AS, atherosclerosis. Arrows in red: promote; text in red: proatherogenic changes; text in green: antiatherogenic changes; text in black word: un-certain effects.

Figure 2

The SCP-x/pro-SCP-2 gene encodes two 13-kDa SCP-2 precursors. The 13-kDa SCP-2 gene can be produced by two sites. One site codes for a precursor 15-kDa pro-SCP-2 protein that undergoes completely post-translationally cleaved to the mature 13-kDa SCP-2 and a 2-kDa peptide. Another site codes for a full-length 58-kDa SCP-x protein, which is partially post-translationally processed into yield a 46-kDa protein and a 13-kDa SCP-2 protein.