Impaired SIRT1 promotes the migration of vascular smooth muscle cell-derived foam cells

Abstract

The formation of fat-laden foam cells, contributing to the fatty streaks of the plaques of atheroma, is the critical early process in atherosclerosis. The previous study demonstrated that vascular smooth muscle cells (VSMCs) contain a much larger burden of the excess cholesterol in comparison with monocyte-derived macrophages in human coronary atherosclerosis, as the main origin of foam cells. It is noteworthy that VSMC-derived foam cells are deposited in subintima but not media, where VSMCs normally deposit in. Therefore, migration from media to intima is an indispensable step for a VSMC to accrue neutral lipids and form foam cell. Whether this migration occurs paralleled with or prior to the formation of foam cell is still unclear. Herein, the present study was designed to test the VSMC migratory capability in the process of foam cell formation induced by oxidized low-density lipoprotein (oxLDL). In conclusion, we provide evidence that oxLDL induces the VSMC-derived foam cells formation with increased migration ability and MMP-9 expression, which were partly attributed to the impaired SIRT1 and enhanced nuclear factor-kappa B (NF-κB) activity. As activation of transient receptor potential vanilloid type 1 (TRPV1) has been reported to have anti-atherosclerotic effects, we investigated its role in oxLDL-treated VSMC migration. It is found that activating TRPV1 by capsaicin inhibits VSMC foam cell formation and the accompanied migration through rescuing the SIRT1 and suppressing NF-κB signaling. The present study provides evidence that SIRT1 may be a promising intervention target of atherosclerosis, and raises the prospect of TRPV1 in prevention and treatment of atherosclerosis.

The role of TRPV1 channels in atherosclerosis

“…SIRT1 is an antiarteriosclerotic factor that can regulate cholesterol metabolism and reduce the inflammatory response [25]. TRPV1 activation by capsaicin can inhibit the formation and migration of VSMC-derived foam cells by protecting SIRT 1 and inhibiting NF-kB signaling [26]. In macrophage-derived foam cells, Zhao et al showed that TRPV1 agonists could upregulate the Figure 2.…”

Serum containing Buyang Huanwu decoction prevents age-associated migration and invasion of human vascular smooth muscle cells by up regulating SIRT1 expression

“…Although a study has reported that BYHWS is involved in a neuron protective role through suppression of the P53 pathway (46), to our knowledge, no previous studies have investigated whether BYHWS directly influences SIRT1 expression. It has been demonstrated that SIRT1's predominate function is in delaying aging and suppressing arterial remodeling (26,27,33). Our further experiments revealed that down regulation of SIRT1 levels by siRNA-knockdown elevated cellular migration/invasion and MMP-2, leading to enhancement in senescent HA-VSMCs.…”

“…A low SIRT1 level contributed to not only an acceleration of cellular senescence but also increased capacity for cellular migration and invasion (25)(26)(27)(28)33). Thus we measured the levels of SIRT1 protein in the Ang II-induced HA-VSMCs.…”

Upregulation of arylsulfatase B in carotid atherosclerosis is associated with symptoms of cerebral embolization

“…This may hold promise as a novel therapeutic approach for carotid atherosclerosis since the SIRT1/AMPK pathway is key to a number of vasculoprotective processes. In particular, SIRT1 is the nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that has been associated with inhibition of the proatherogenic VSMC foam cell formation possibly through the suppressing of the nuclear factor kappa B (NF-κB) signalling pathway 38 . AMPK is the main energy-sensing kinase in all eukaryotic cells and has been implicated in stabilizing atherosclerotic plaques through the inhibition of the mammalian target of rapamycin (mTOR) signalling pathway 39 .…”