Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis

Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress. The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA.

Isolated Dissection of the Ductus Arteriosus Associated with Sudden Unexpected Intrauterine Death

We report five cases of sudden intrauterine death due to premature closure of the ductus arteriosus. In four cases, this was caused by dissecting the hematoma of the ductus arteriosus with intimal flap and obliteration of the lumen. In one case, the ductus arteriosus was aneurysmatic, with lumen occlusion caused by thrombus stratification. No drug therapy or free medication consumption were reported during pregnancy. The time of stillbirth ranged between 26 and 33 gestational weeks. We performed TUNEL analysis for apoptosis quantification. The dissecting features were intimal tears with flap formation in four of the cases, just above the origin of the ductus arteriosus from the pulmonary artery. The dissecting hematoma of the ductus arteriosus extended downward to the descending aorta and backward to the aortic arch with involvement of the left carotid and left subclavian arteries. TUNEL analysis showed a high number of apoptotic smooth muscle cells in the media in two cases. Abnormal ductal remodeling with absence of subintimal cushions, lacunar spaces rich in glycosaminoglycans (cystic medial necrosis), and smooth muscle cell apoptosis were the pathological substrates accounting for failure of remodeling process and dissection.

Effects of Liposomal Simvastatin Nanoparticles on Vascular Endothelial Function and Arterial Smooth Muscle Cell Apoptosis in Rats with Arteriosclerotic Occlusive Disease of Lower Limb via P38 Mitogen-Activated Protein Kinase Nuclear Factor Kappa-B Pathway

This article prepared a simvastatin-NLCs for the treatment of arteriosclerotic occlusive disease of lower limbs. Taking the size distribution, polydispersity coefficient, encapsulation efficiency and drug loading of simvastatin-NLCs as evaluation indicators, various prescription factors of simvastatin-NLCs were investigated. The in vitro release behavior and stability of simvastatin-NLCs were also investigated. A hyperlipidemia rat model was established using high-fat diets. SD rats fed ordinary diet were set as normal control groups. 20 rats, 20 in the simvastatin group and 20 in the simvastatin nanocarrier group. After 5 weeks of drug intervention, the rats were sacrificed and the aorta was taken to determine the smooth muscle cell apoptosis rate. Studies have shown that simvastatin nanocarriers can more effectively reduce blood lipids in hyperlipidemia rats, increase the rate of smooth muscle cell apoptosis in hyperlipidemia rats, and delay the onset of atherosclerosis.

Apoptosis Sel Otot Rangka dan Perubahan Berat Badan pada Tikus Diabetes yang Diberi Ekstrak Umbi Bawang Dayak (Eleutherine palmifolia L., Merr)

This study was undertaken to investigate the antidiabetic and antioxidant of bawang dayak bulbs (Eleutherine palmifolia L., Merr) extract (BDBE) on skeletal muscle cell apoptosis and body weight change in diabetic rat. Single doses alloxan 120 mg/kgBW were administered intraperitoneally to get diabetic rat. Twenty four male Wistar rat of three months old were used in this study. Rat were devided into six groups: negative control group (were not diabetic and treated) (K0), positive control group (were diabetic and treated CMC-Na) (K1), drug control group (were diabetic and administrated metformin as a standard drug) (K2), BDBE dosed 200 (P1), 400 (P2), and 800 mg/kgBW (P3). The treatment was conducted for 14 days. Hypoglycemic effect and body weight measured of all mice was determined at day 7 and 14 of treatment. At the end of research, all of rat were sacrificed and m. gastrocnemius were collected for apoptosis analysis by TUNEL staining and atrophy analysis by Hematoxilin-Eosin staining. The result of this study showed that BDBE decreased skeletal muscle cell apoptosis and mantained the skeletal muscle fiber diameter (atrophy) and body weight change in diabetes rat.