Association between α1-antitrypsin and acute coronary syndrome.

α1-antitrypsin (AAT) is a protein released as part of the anti-inflammatory response. It regulates the activity of serine proteinases and has a crucial role in the pathogenesis of acute coronary syndrome (ACS). The present study aimed to examine its role in patients with ACS. The plasma samples of 117 patients were collected at the Cardiology Department of the Affiliated Hospital of Youjiang Medical University (Baise, China). These included 46 cases of ACS (who met the diagnostic criteria for ACS and had ≥50% luminal stenosis of any coronary vessel), 35 cases of stable angina (SA; with ≥50% luminal stenosis of any coronary vessel but in a stable condition) and 36 normal healthy controls (subjects with no luminal stenosis in their coronary arteries). Plasma AAT protein concentrations were measured by ELISA and clinical data were collected. The plasma levels of AAT protein in patients with ACS were lower than those in controls and cases of SA (P<0.05), and the levels tended to decrease with the number of coronary artery lesions involved. There were no significant associations of the expression of plasma AAT protein and the number of diseased vessels in patients or the degree of stenosis. There was no correlation between the plasma protein levels of AAT and Gensini scores of patients with ACS. In conclusion, the plasma AAT protein levels in patients with ACS may contribute to the occurrence and development of coronary artery disease.

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people.

This study aimed to investigate genetic polymorphisms of miR-146a, miR-149, miR-196a2, and miR-499 and genetic susceptibility of ischemic stroke in the population of Guangxi in China. A case-control study was used to investigate miRNAs genetic polymorphisms in 298 patients with ischemic stroke and 303 healthy controls. Single-base extension polymerase chain reaction genotyping principle was used to detect genetic polymorphisms of miRNAs,and the relationship of genotype in each group and blood lipid was compared and analyzed. The genetic polymorphism of miR-499A>G (rs3746444) was associated with ischemic stroke (P < 0.05), and the risk of ischemic stroke was high in patients with G allele (OR = 1.455; 95% CI = 0.531-2.381; P = 0.039) and AG (OR = 1.339; 95% CI = 1.126-1.967; P = 0.037) genotype. The levels of low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, homocysteine, and lipoprotein in the ischemic stroke group were higher than those in the control group (P < 0.05). The genetic polymorphism of miR-499A>G (rs3746444) was related to ischemic stroke, and G allele and AG genotype may increase the risk of ischemic stroke in the population of Guangxi in China.

Api6/AIM/Spα/CD5L overexpression in alveolar type II epithelial cells induces spontaneous lung adenocarcinoma.

Chronic inflammation is an important contributor to the development of lung cancers, one of the most common malignancies worldwide, but the underlying molecular mechanisms of inflammation that specifically cue cancer risk remain poorly understood. Apoptosis inhibitor 6 (Api6, also known as AIM, Sp-α, and CD5L) is a downstream target gene of neutral lipids and peroxisome proliferator-activated receptor gamma in lung alveolar type II (AT II) epithelial cells. An association among increased expression of Api6 in certain settings of pathogenic lung inflammation in mice prompted us to hypothesize a possible role in cancer. Here, we report that Api6 promotes malignant transformation by limiting lung epithelial cell apoptosis and promoting immune escape. The specific function of Api6 in AT II cells was determined by using a doxycycline-inducible Api6 mouse model. Api6 overexpression inhibited apoptosis and activated oncogenic signaling in AT II lung epithelial cells, inducing emphysema and adenocarcinoma. In addition, Api6 overexpression in AT II cells increased the concentrations of proinflammatory cytokines/chemokines in bronchoalveolar lavage fluid and serum, promoting expansion of myeloid-derived suppressor cells (MDSC) in lung and blood but not in bone marrow or spleen. Lung MDSCs suppressed T-cell proliferation and activity in vitro and reduced levels of T cells in vivo following doxycycline treatment to activate Api6. Together, our findings establish that Api6 promotes lung tumorigenesis by blocking a mechanism of epithelial apoptosis that would normally support immunosurveillance.