RESUMO
Atherosclerosis is a common type of cardiovascular disease (CVD), remaining one of the leading causes of global death. Tripartite motif-containing 28 (TRIM28) is a member of TRIM family that has been found to be involved in atherosclerosis. However, the role of TRIM28 in atherosclerosis remains unknown. This study aimed to investigate the effects of TRIM28 on the phenotypic switching of human aortic smooth muscle cells (HASMCs), which is considered as a fundamental event during the development of atherosclerosis. The results showed that TRIM28 was highly expressed in human atherosclerotic tissues, as well in cultured HASMCs stimulated by platelet-derived growth factor subunit B homodimer (PDGF-BB). Knockdown of TRIM28 by transfection with siRNA targeting TRIM28 (si-TRIM28) significantly suppressed the PDGF-BB-induced cell proliferation and migration of HASMCs. Besides, knockdown of TRIM28 inhibited the expressions of matrix metalloproteinase (MMP)-2 and MMP-9. The VSMC markers including α-smooth muscle actin (α-SMA), calponin and SM22α were upregulated in TRIM28 knocked down HASMCs. Furthermore, knockdown of TRIM28 blocked PDGF-BB-induced NF-κB activation in HASMCs. Collectively, knockdown of TRIM28 prevented PDGF-BB-induced phenotypic switching of HASMCs, which might be mediated by the regulation of NF-κB signaling pathway.
Assuntos
Becaplermina/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteína 28 com Motivo Tripartido/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Proteínas dos Microfilamentos/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator de Transcrição RelA/metabolismo , Proteína 28 com Motivo Tripartido/antagonistas & inibidores , Proteína 28 com Motivo Tripartido/genética , Regulação para Cima/efeitos dos fármacos , CalponinasRESUMO
BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) has been proposed an independent risk factor for coronary heart disease (CHD). However, the magnitude of this association in the general population varied considerably. OBJECTIVE: To investigate the association of baseline non-HDL-C level with CHD risk in the general population by conducting a meta-analysis. METHODS: A comprehensive literature search was performed in the Pubmed and Embase until January 2017. Prospective observational studies that investigated the association between baseline non-HDL-C level and CHD risk in the general population were included. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated for the highest vs. the lowest non-HDL-C category. RESULTS: Seven articles with 9 independent prospective studies involving 448,732 individuals were included. Meta-analysis showed that individuals with the highest non-HDL-C level at baseline were associated with greater risk of CHD (RR 1.79; 95% CI 1.68-1.91) than those in the lowest non-HDL-C level category. Subgroup analysis suggested that the risk of CHD seemed more pronounced among men (HR 1.98; 95% CI 1.70-2.30) than among women (HR 1.63; 95% CI 1.35-1.96). CONCLUSIONS: Higher baseline non-HDL-C level is associated with increased risk of CHD in the general population. This risk seems more pronounced in men than in women. However, gender difference in non-HDL-C level associated with CHD risk should be verified by more well-designed prospective studies.