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Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy.

The Niemann-Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.

It has been reported that oxidized low-density lipoprotein (Ox-LDL) can increase the expression of adipophilin. However, the detailed mechanisms are not fully understood. The aim of this study was to investigate the mechanism of Ox-LDL on adipophilin expression and the intracellular lipid droplet accumulation. A mouse macrophage-like cell line, RAW264.7, was used throughout, and it was found that Ox-LDL induced adipophilin expression in a dose-dependent manner. Moreover, Ox-LDL induced peroxisome proliferator-activated receptor-gamma (PPARgamma) expression and PPARgamma-specific inhibitor T0070907 abrogated Ox-LDL-induced adipophilin expression, but specific agonist GW1929 not. Furthermore, Ox-LDL induced phosphorylation of ERK1/2, and ERK1/2-specific inhibition by PD98059 suppressed the Ox-LDL-induced PPARgamma and adipophilin expression. The results showed that ERK1/2 or PPARgamma-specific inhibition decreased the amounts of intracellular lipid droplets. Meanwhile, the PPARgamma-specific agonist increased intracellular lipid droplets. These results suggested that Ox-LDL-induced increase in adipophilin level via ERK1/2 activation is one of the mechanisms of inducing greater amounts of intracellular lipid droplets in RAW264.7 cells, which indicated that adipophilin is involved in atherosclerotic progression.

Improvement of blood flow and promotion of neovascularization are important therapeutic measures for ischemic peripheral vascular diseases.Since apolipoproteinA(ApoA) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen(Plg),ApoA may also have a negative effect on endothelial progenitor cell(EPC)-induced vasculogenesis through Plg-like inhibitory effects on EPC proliferation,adhesion,migration and vasculogenesis.To evaluate the effect of ApoA on EPCs-induced vasculogenesis.ApoA was stably expressed and prepared from COS-7 cell line which were transfected with the expression plasmids pSG-5 encoding human ApoA cDNA,then purified by immunoaffinity chromatography;EPCs were isolated from the bone marrow of ApoA transgenic mice,wild-type litter mates and normal mice.These cells were cultured without or with ApoA before transplantation.Hindlimb ischemia models were surgically induced in mice,which then received an intravenously injection of 3 ×105 EPCs.At 3,7 and 14 days post EPC transplantation,the adhesion,migration abilities and capillary density in calf muscles were assessed.Results indicate that ApoA significantly reduced the adhesion and migration abilities of EPCs.Furthermore,the tubule-like formation of EPCs on Matrigel gels was damaged.In vivo experiments showed the number of EPCs home to ischemic peripheral vascular,and the number of capillary vessels decreased significantly in ApoA transgenic mice.This study demonstrated that ApoA could attenuate the adhesion,migration,and homing abilities of EPCs and could impair the vasculogenesis ability of EPCs.