SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis

Abstract

Atherosclerosis, which underlies life-threatening cardiovascular disorders including myocardial infarction and stroke 1 , is initiated by low density lipoprotein cholesterol (LDL) passage into the artery wall and engulfment by macrophages, leading to foam cell formation and lesion development 2, 2, 3, 3 . How circulating LDL enters the artery wall to instigate atherosclerosis is unknown. Here we show in mice that scavenger receptor, class B type 1 (SR-B1) in endothelial Reprints and permissions information is available at www.nature.com/reprints.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis

“…Many recent reviews have discussed the pathogenesis of atherosclerosis and the readers are therefore directed to these for more details . Briefly, the accumulation of LDL in the subendothelial space, either via passive diffusion or scavenger receptor (SR)‐B1‐driven transcytosis, triggers an inflammatory response and activation or dysfunction of the endothelium . The endothelial cells in such a state express a range of adhesion molecules and chemokines that aids in the recruitment of circulating leukocytes, particularly monocytes, to the site of LDL accumulation .…”

Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

“…Raji B cells were grown in DMEM supplemented with 20% FBS and 2 mM L-glutamine. In order to generate stable knock-down lines of SR-B1, HBE cells were transduced with lentivirus containing the appropriate shRNA cloned into pLKO.1 (Addgene 10878) as described previously (Huang et al, 2019). Transduced cells were selected with puromycin (Sigma-Aldrich P8833-10MG) and surviving cells were maintained in puromycin for three additional passages.…”

Scavenger Receptor Class B type 1 (SR-B1) and the modifiable risk factors of stroke

“…However, a recent article suggests that SR-B1 may have polarizing roles in atherosclerosis. Huang et al presented a study implying that SR-B1 drives endothelial cell LDL transcytosis through a dynamic partnership with dedicator of cytokinesis 4, which will promote atherosclerosis [33]. Conversely, this same study provided conflicting information, in which they also found that the selective silencing of SR-B1 expression in hepatocytes resulted in more severe atherosclerosis and early death [33].…”

“…SR-B1's other diverse functions also include pathogen recognition [22], protective effects against infertility in women [23], and lastly, efferocytosis of apoptotic cells, contributing to its anti-inflammatory characteristics [24]. These receptors are widely dispersed and expressed in various tissue and cell types, such as in the intestines, keratinocytes, epithelial cells, smooth muscle cells, monocytes, macrophages, mast cells, placenta, gallbladder, ocular tissues, endothelial cells, steroidogenic cells, astrocytes, neurons, hepatocytes, and adipocytes [16,[25][26][27][28][29][30][31][32][33]. The cell types that express SR-B1 and their functions pertaining to stroke and other neurological disorders have been summarized in Table 1.…”