Mac-1 deficiency ameliorates pressure overloaded heart failure through inhibiting macrophage polarization and activation.

Persistent pressure overload commonly leads to pathological cardiac hypertrophy and remodeling, ultimately leading to heart failure (HF). Cardiac remodeling is associated with the involvement of immune cells and the inflammatory response in pathogenesis. The macrophage-1 antigen (Mac-1) is specifically expressed on leukocytes and regulates their migration and polarization. Nonetheless, the involvement of Mac-1 in cardiac remodeling and HF caused by pressure overload has not been determined. The Mac-1-knockout (KO) and wild-type (WT) mice were subjected to transverse aortic constriction (TAC) for 6 weeks. Echocardiography and pressure-volume loop assessments were used to evaluate cardiac function, and cardiac remodeling and macrophage infiltration and polarization were estimated by histopathology and molecular techniques. The findings of our study demonstrated that Mac-1 expression was markedly increased in hearts subjected to TAC treatment. Moreover, compared with WT mice, Mac-1-KO mice exhibited dramatically ameliorated TAC-induced cardiac dysfunction, hypertrophy, fibrosis, oxidative stress and apoptosis. The potential positive impacts may be linked to the inhibition of macrophage infiltration and M1 polarization via reductions in NF-kB and STAT1 expression and upregulation of STAT6. In conclusion, this research reveals a new function of Mac-1 deficiency in reducing pathological cardiac remodeling and HF caused by pressure overload. Additionally, inhibiting Mac-1 could be a potential treatment option for patients with HF in a clinical setting.

[Comparative study of APOB gene 3'VNTR polymorphisms between natural longevity and controls in Uighur nationality].

OBJECTIVE: To investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people. METHODS: Totally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing. RESULTS: Fourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing. CONCLUSION: These results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.