Proatherogenic Flow Increases Endothelial Stiffness via Enhanced CD36-Mediated Uptake of Oxidized Low-Density Lipoproteins

Abstract

DF facilitates endothelial CD36-dependent uptake of oxidized lipids resulting in local increase of endothelial stiffness in proatherogenic areas of the aorta.

Daily melatonin protects the endothelial lineage and functional integrity against the aging process, oxidative stress, and toxic environment and restores blood flow in critical limb ischemia area in mice

“…In fact, abundant data have shown that the initiation and propagation of endothelial cell (EC) dysfunction in the coronary artery are the fundamental mechanism for the development of arteriosclerosis, followed by plaque formation and ultimately, plaque fissuring and rupture, resulting in acute obstructive syndrome . A large number of studies have reported that inflammation, generations of oxidative stress/free radicals, and oxidized low‐density lipoprotein (LDL) as well as aging are crucial contributors to the initiation and propagation of EC dysfunction . Thus, early interventions (ie, primary prevention) using health supplements to prevent and alleviate endothelial dysfunction may be a feasible approach.…”

“…14,[18][19][20] A large number of studies have reported that inflammation, 14,[18][19][20] generations of oxidative stress/free radicals, and oxidized low-density lipoprotein (LDL) as well as aging are crucial contributors to the initiation and propagation of EC dysfunction. [21][22][23][24][25] Thus, early interventions (ie, primary prevention) using health supplements to prevent and alleviate endothelial dysfunction may be a feasible approach.…”

Endothelial stiffening in dyslipidemia

“…(ii) OxLDL-induced disruption of lipid packing paradoxically is associated with EC stiffening via activation of the contractile RhoA/ROCK cascade, whereas enriching the cells with cholesterol has a rescue effect [3]. (iii) OxLDL-induced stiffening of aortic endothelial cells critically depends on a scavenger receptor CD36 [3,4], known to bind oxLDL and mediate its inflammatory effects [5]. Most recently, we demonstrated that there is a strong synergistic interaction between oxLDL/plasma dyslipidemia and proatherogenic disturbed flow in exacerbating endothelial stiffening via increased expression of CD36 and uptake of oxidized lipids in regions exposed to proatherogenic flow [4].…”

“…(iii) OxLDL-induced stiffening of aortic endothelial cells critically depends on a scavenger receptor CD36 [3,4], known to bind oxLDL and mediate its inflammatory effects [5]. Most recently, we demonstrated that there is a strong synergistic interaction between oxLDL/plasma dyslipidemia and proatherogenic disturbed flow in exacerbating endothelial stiffening via increased expression of CD36 and uptake of oxidized lipids in regions exposed to proatherogenic flow [4]. Specifically, we showed that there is increased stiffening in the endothelial monolayer of the freshly isolated mouse aortic arch as compared to the athero-resistant region of the descending aorta.…”

“…Specifically, we showed that there is increased stiffening in the endothelial monolayer of the freshly isolated mouse aortic arch as compared to the athero-resistant region of the descending aorta. A short-term high fat diet exasperated endothelial stiffening, an effect attributed to the synergistic interaction of pro-atherogenic disturbed flow and increased uptake of oxidative low-density lipoprotein (oxLDL) [4].…”