Effect of miR-663 on atherosclerosis by regulating the proliferation of vascular smooth muscle cells in lipid plaques.

OBJECTIVES: Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. microRNAs (miRNAs) are widely distributed in the human body and closely related to the pathological progress of AS. This study probed into the function of miR-663 in AS. METHODS: The atherosclerotic plaques, cholesterol (CHOL), low-density lipoprotein (LDL), inflammatory factors, and miR-663 expression in ApoE-/- mice on high-fat diet were evaluated. The overexpressing miR-663 adenovirus was injected into ApoE-/- mice, followed by measurement of type III collagen (Col III), matrix metalloproteinase (MMP)-2, α-SMA, osteopontin, and CD31. miR-663 mimic or inhibitor was introduced into vascular smooth muscle cells (VSMCs) stimulated by oxidized LDL (Ox-LDL), and cell proliferation and IL-6 and IL-18 secretion were evaluated. The binding relationship between miR-663 and HMGA2 was verified, followed by the determination of HMGA2 role in VSMC proliferation. RESULTS: Atherosclerotic plaques appeared in ApoE-/- mice on high-fat diet, with increased CHOL, LDL, osteopontin, MMP-2 and Col III and decreased miR-663, α-SMA and CD31. miR-663 overexpression downregulated osteopontin, MMP-2 and Col III and upregulated α-SMA and CD31 in ApoE-/- mice on high-fat diet. With Ox-LDL concentration increase, VSMC proliferation was promoted and miR-663 was downregulated. miR-663 overexpression inhibited proliferation of Ox-LDL-stimulated VSMCs and reduced levels of inflammatory factor levels, whereas silencing miR-663 did the opposite. miR-663 targeted HMGA2. HMGA2 overexpression partially reversed the inhibitory effect of miR-663 overexpression on VSMC proliferation. CONCLUSION: miR-663 targeted HMGA2 to inhibit VSMC proliferation and AS development, which may offer insights into AS treatment.

Synergistic effects of telmisartan and pyridoxamine on early renal damage in spontaneously hypertensive rats.

The aim of this study was to investigate the protective effects of telmisartan and/or pyridoxamine on spontaneously hypertensive rats (SHRs). Rats were treated with telmisartan (T group) or pyridoxamine (P group), or telmisartan and pyridoxamine (TP group). The serum levels of advanced glycation end products (AGEs), superoxide dismutase (SOD), malonaldehyde and the level of 24-h urinary albumin were measured. Morphological changes in renal tissues were observed under light (H&E or Masson's trichrome) and transmission electron microscopy. Expression of NF-κBp65 and p-ERK1/2 in renal tissue was detected by immunohistochemistry. Expression of receptors for advanced glycation end products (RAGE) and TGF-ß in the renal cortex was investigated by western blotting. We found that early renal structural and functional damage was alleviated in the three intervention groups. SOD activity was significantly elevated in the P and TP groups (P<0.05) compared to that in the T group. Of note, both the positive expression of NF-κBp65 (P<0.01 vs. the T and P groups) and p-ERK1/2 (P<0.05 vs. the P group) was lowest in the TP group. Our results suggest that the combined use of telmisartan and pyridoxamine is superior to the single use of either drug on renoprotection, which may result from the alleviation of oxidative stress and the reduction of NF-κBp65 and p-ERK1/2 activation.