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Angiopoietin-2 has been reported to regulate the inflammation process, which is associated with recurrence of stroke. The purpose of this study was to test the hypothesis that plasma levels of angiopoietin-2 and variants of angiopoietin-2 will confer risk of stroke recurrence. The association of plasma angiopoietin-2 (determined by using ELISA) and the variants in angiopoietin-2 promoter with stroke recurrence was tested in 1735 patients with stroke of three subtypes, lacunar infarct (n = 475), atherothrombotic (n = 794) and hemorrhage (n = 466), for a period of following-up 4.5 years (mean), the association was evaluated by using Kaplan–Meier analysis and the Cox regression models. We found that angiopoietin-2 levels were associated with risk of stroke recurrence in lacunar infarct patients. Taking the lowest quartile as reference, the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for stroke recurrence was 1.48 (0.74–2.95) for the second quartile, 2.56 (1.35–4.86) for the third and 2.15 (1.11–4.17) for the fourth. Allele T of rs3739391 in angiopoietin-2 promoter was associated with elevated angiopoietin-2 levels and increased risk of stroke recurrence in patients with lacunar infarct with HR 1.67 (1.06–2.63) relative to the allele C, but neither in those with atherothrombotic nor in those with hemorrhagic stroke. Our results indicate that both angiopoietin-2 and allele T of rs3739391 might be the risk marker for stroke recurrence in the patients with lacunar infarction. These findings may help to improve future prevention or therapy strategies for stroke. Even some conventional risk factors have been identified responsible for stroke recurrence, but these factors could not fully explain all the recurrent stroke events. Our study opens a new page for the first time that angiopoietin/tie2 pathway has a potential role in lacunar stroke recurrence. Since several strategies are available for blocking or neutralizing plasma angiopoietin-2, especially eicosapentaenoic acid rich in sea food. Our finding obviously has its clinical implication if it was proved by large, prospective clinical studies.

Mitogen-activated protein kinase kinase 7 (MKK7) induces cardiac hypertrophy by activating the c-Juns NH2-terminal kinases (JNK). It has been reported that growth arrest and DNA-damage-inducible beta (GADD45Β) binds to MKK7 directly and blocks its catalytic activity, mediates the inhibition of JNK signaling. However, the potential role of GADD45Β on cardiac hypertrophy has not been investigated. In this study, we found co-infection of cardiomyocytes with adenoviral vectors expressing MKK7 and GADD45B could counteract the characteristic hypertropic responses, including an increase in cell size and elevated atrial natriuretic factor (ANP) expression which induced by overexpression of MKK7. Furthermore, siRNA-mediated knockdown of GADD45B could also cause cardiomyocytes hypertrophy. GeneChip data showed that GADD45B mRNA decreased significantly in patients with hypertrophy cardiomyopathy (HCM) compared with healthy subjects. Association study indicated that haplotype (rs2024144–rs3783501) of GADD45B affected the thickness of inter-ventricular septum in patients with HCM. Dual-luciferase assay showed that C–A haplotype displayed significantly increased transcription activity compared to T–G haplotype.

Purpose Perilipin coats lipid droplets in adipocytes and steroidogenic cells. Its major role is in the regulation of intracellular lipolysis in adipocytes. Our aim was to examine the association between common variants at the PLIN1 gene and central obesity in unrelated Chinese adults. Methods A case-control study was carried out on 869 patients with central obesity and 869 age- and gender-matched individuals without central obesity. Two PLIN1 variants (rs6496589 and rs8179078) were genotyped by PCR and restriction enzyme analysis. In addition, the association of the variant with central obesity was replicated in an independent population of 629 central obesity patients and 518 controls. Finally, the relationship between rs6496589 and enhancing lipid accumulation in THP-1-derived macrophages was assessed. Results PLIN1 rs6496589 allele frequencies and genotype frequencies of CG + GG in the patients’ group were much lower than those in the control group. After adjustment for conventional risk factors using multiple logistical regression analysis, rs6496589G allele frequencies were significantly associated with a lower risk of central obesity (OR 0.71, 95% CI: 0.59–0.86, P = 0.001). These results were confirmed in an independent study. No association was found between PLIN1 rs8179078 and central obesity. Furthermore, in vitro assays revealed that homozygous rs6496589G alleles presented lower lipid droplet accumulation in THP-1-derived macrophages, compared with non-carriers. Conclusions The functional PLIN1 rs6496589 may influence the risk of central obesity through possible regulation of lipid storage.

A new gene (GenBank Accession No. AF114264) was cloned from umbilical vein wall tissue by using RT-PCR. The gene shares high similarity to the gene encoding F-actin binding protein nexilin, so named as NELIN. A clone of 2737bp contains open reading frame of 1344bp extending from 412 to 1755. NELIN was expressed primarily in the heart and skeletal muscle among eight tested normal tissues. Immunofluorescence and immunoprecipitation demonstrated that NELIN product was associated with F-actin. Stable transfection of NELIN into HeLa cells increased the cell migration by 2.17-fold and the adhesion by 1.67-fold, respectively, compared to cells with the empty vector (P0.05). The results support that NELIN product is an F-actin associated protein and mediates cell motility.

Many CARD-containing caspase mediators interact with CARD-containing caspases and participate in activation or suppression of caspases. We cloned a novel CARD-containing protein from our EST database, named CARP. Computational characterization revealed that CARP encoded 445 amino acids with predicted MW 49.7 kDa, localized at chromosome 10p13 with 15 exons, and four putative function domains, one CARD domain (aa 160-243), one nuclear receptor-binding motif, two EF-hand motifs, and 42% alpha-helix content. Stable transfection of CARP into lung carcinoma A549 and HEK293S cells leads to 23% of the cells undergoing apoptosis, but only 3% in the cells transfected with empty control vector. The cell proliferation was significantly inhibited by 1.2-5 folds (P

C53, cloned from rat brain cDNA library, can bind to p35, the precursor of activator of Cdk5. A novel gene with 84% homolog to C53, named IC53, was cloned from our 5300 EST database of human aorta cDNA library (GenBank Accession No. AF110322). Computational analysis showed that IC53 cDNA is 2538 bp long, encoding 419 amino acids, mapped to chromosome 17q21.31 with 12 exons, ubiquitously expressed in 12 tested normal tissues and 8 tumor cell lines from MTN membranes and vascular endothelial cells by Northern blot and in situ hybridization, and upregulated in the rat models of subacute heart failure and chronic ischemic heart failure by left coronary ligation. Stable transfection of IC53 stimulates ECV304 cell proliferation by 2.1-fold compared to cells with empty vector (P0.05). The results support that IC53 is a novel gene, mainly expressed in vascular endothelial cells and mediates cell proliferation.