miR-33a Expression Attenuates ABCA1-Dependent Cholesterol Efflux and Promotes Macrophage-Like Cell Transdifferentiation in Cultured Vascular Smooth Muscle Cells.
Ikechukwu C EsobiOlanrewaju OladosuJing Echesabal-ChenRhonda R PowellTerri BruceAlexis StamatikosPublished in: Journal of lipids (2023)
Recent evidence suggests that the majority of cholesterol-laden cells found in atherosclerotic lesions are vascular smooth muscle cells (VSMC) that have transdifferentiated into macrophage-like cells (MLC). Furthermore, cholesterol-laden MLC of VSMC origin have demonstrated impaired ABCA1-dependent cholesterol efflux, but it is poorly understood why this occurs. A possible mechanism which may at least partially be attributed to cholesterol-laden MLC demonstrating attenuated ABCA1-dependent cholesterol efflux is a miR-33a expression, as a primary function of this microRNA is to silence ABCA1 expression, but this has yet to be rigorously investigated. Therefore, the VSMC line MOVAS cells were used to generate miR-33a knockout (KO) MOVAS cells, and we used KO and wild-type (WT) MOVAS cells to delineate any possible proatherogenic role of miR-33a expression in VSMC. When WT and KO MOVAS cells were cholesterol-loaded to convert into MLC, this resulted in the WT MOVAS cells to exhibit impaired ABCA1-dependent cholesterol efflux. In the cholesterol-loaded WT MOVAS MLC, we also observed a delayed restoration of the VSMC phenotype when these cells were exposed to the ABCA1 cholesterol acceptor, apoAI. These results imply that miR-33a expression in VSMC drives atherosclerosis by triggering MLC transdifferentiation via attenuated ABCA1-dependent cholesterol efflux.
Keyphrases
- induced apoptosis
- low density lipoprotein
- cell cycle arrest
- poor prognosis
- long non coding rna
- cell proliferation
- vascular smooth muscle cells
- oxidative stress
- cardiovascular disease
- adipose tissue
- cell death
- long noncoding rna
- drug delivery
- endoplasmic reticulum stress
- angiotensin ii
- signaling pathway
- stem cells
- type diabetes
- high resolution
- endothelial cells
- pi k akt
- wild type
- cancer therapy