Regulation of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by destruction and progressive expansion of the abdominal aortic wall. An AAA is typically defined as an enlargement of the abdominal aorta with diameter ≥3 cm or ≥50% greater than the suprarenal diameter. The pathological changes associated with AAA include inflammatory cell infiltration, extracellular matrix (ECM) destruction and remodeling, and vascular smooth muscle cell loss. The matrix metalloproteinase (MMP) family of proteins plays an important role in initiation and progression of AAA. Since understanding the regulation of MMP-2 and MMP-9 in AAA is essential for treatment of AAA, this review summarized the regulatory mechanisms of MMPs to provide a reference for exploring novel therapeutic approaches.

Effects of Omega-3 Fatty Acids on Chinese Patients with Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis

Objective:Fish oil(FO)contains omega-3 that inhibits inflammation and blood lipid metabolism,giving it a protective cardiovascular effect.Due to dietary habits,a majority of large-scale clinical trials examining FO and cardiovascular health have been conducted in the Caucasian populations.However,the effects of FO on cardiovascular inflammation indicators and blood lipid metabolism in the Chinese population remain unclear.This study aimed to perform a meta-analysis to elucidate the impact of FO on cardiovascular health in the Chinese population.Methods:Web searches were utilized to locate records of clinical trials related to cardiovascular health and consumption of FO capsules or fish containing omega-3 in several databases,including PubMed,Medline,Embase,Cochrane Library,CNKI,and ClinicalTrial.gov,etc.We obtained lipid metabolism and related proinflammatory markers as the study outcome.We used Review Manager 5.4 and Stata 16 for the statistical analysis.If the I^(2)≥30%,a random effects model was used,and if the I^(2)<30%,a fixed effects model was used.Results:Twenty eligible trials were shortlisted from>1000 records.The meta-analysis revealed that supplementation with eicosapentaenoic acid and docosahexaenoic acid reduced systolic blood pressure by 1.88 mmHg(95%CI:4.97 to1.20,P=0.23),diastolic blood pressure by 0.86 mmHg(95%CI:1.79 to 0.06,P=0.07),fasting blood glucose by 0.05 mmol/L(95%CI:0.16 to 0.06,P=0.40),and low-density lipoprotein-cholesterol by 0.12 mmol/L(95%CI:0.23 to0.01,P=0.04),when compared to placebo.However,these supplements increased high-density lipoprotein-cholesterol by 0.03 mmol/L(95%CI:0.01 to 0.05,P<0.001),when comparedto placebo.Dose subgroup analyses examiningtotal cholesterol foundthatthe low-dose group(mean difference=0.44,95%CI:0.55 to0.34,P<0.001)demonstrated the best results.Further,results from dose subgroup analyses showed that the all-dose group demonstrated a decrease in tumor necrosis factor(TNF-a)levels among the study subjects,when compared to other groups.Conclusions:Consumption of FO containing omega-3 fatty acids in the Chinese population can improve lipid metabolism and reduce levels of proinflammatory markers.Therefore,it is necessary to vigorously promote the benefits of consuming FO to prevent cardiovascular diseases throughout China.

Cardioprotective Effect of Growth Differentiation Factor 15 Against Isoproterenol-Induced Cardiomyocyte Apoptosis via Regulation of the Mitochondrial Fusion

Objective:Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure(HF).Growth differentiation factor 15(GDF15)dramatically increases during cardiac hypertrophy and dysfunction,but its functions and mechanisms are barely known.This study aims to elucidate the role and mechanism of GDF15 in HF.Methods:Between January 2017 and August 2018,57 patients diagnosed with chronic HF(aged>18 years,with left ventricular ejection fraction(LVEF)35%)and 57 non-HF patients(aged>18 years,LVEF>35%)were prospectively enrolled in this study based on the balance of the baseline characteristics.Other acute or chronic diseases and pregnant/lactating women were excluded.The serum concentrations of GDF15 were detected.Isoproterenol(ISO)-induced HF mouse model was established by pumping with ISO(30mg/(kg·day))for 4 weeks,and the GDF15 expression in serum and heart tissue was evaluated in vivo.Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage.The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro.Results:After adjusting the baseline characteristic,serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients.Similarly,in the ISO-induced HF mouse model,the significant increase in GDF15 was associated with the process of HF in vivo.Moreover,the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model.Furthermore,using primary cardiomyocytes,we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model.Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress.In contrast,the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage.Conclusions:GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF.These findings indicate that GDF15 may be a potential therapeutic target for HF.

A novel function of CREG in metabolic disorders

Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment.Cellular repressor of E1A-stimulated genes(CREG)is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature,homeostatic state.Recently,CREG turns to be an important mediator in the development of metabolic disorders.Here in this review,we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.