The Seed Coat Extract of Black Soybean Decreases Nicotine-Induced Vascular Fiber Degradation by Suppressing Matrix Metalloproteinase 2 Expression.

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of vascular walls and progressive dilation of the abdominal aorta. Nicotine, the main component of tobacco, is reportedly associated with the development and rupture of AAA. It is desirable to attenuate the destructive effect of nicotine on vascular walls, using dietary food components. However, effective methods for preventing AAA progression using dietary food components remain unestablished. This study focuses on proanthocyanidins, well known for their potent antioxidant activity. We speculated that proanthocyanidins can suppress nicotine-induced weakening of vascular walls. To estimate the effect of black soybean seed coat extract (BSSCE), rich in proanthocyanidins, on nicotine-induced weakening of the aortic wall, mice were divided into four groups: the control diet and distilled water group (named C), BSSCE solution diet and distilled water group (named B), control diet and 0.5 mg/mL nicotine solution group (named CN), and BSSCE solution diet and 0.5 mg/mL nicotine solution group (named BN). Nicotine-induced degradation of elastin and collagen fibers were significantly suppressed in BN group. The positive areas for matrix metalloproteinase (MMP)-2 and oxidative stress in BN group were significantly decreased compared to those in CN group. These results suggest that proanthocyanidins-rich BSSCE can prevent the weakening of the aortic wall via inhibiting MMP-2 upregulation.

Dietary DNA Attenuates the Degradation of Elastin Fibers in the Aortic Wall in Nicotine-Administrated Mice.

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Epidemiologic data have clearly linked tobacco smoking to aneurysm formation and a faster rate of expansion. It suggested that nicotine, one of the main ingredients of tobacco, has been suggested to be associated with AAA development and rupture. In the condition where no established drugs are available; therefore, an effective approach to prevent the vascular damage from nicotine consumption may be the use of dietary functional food factors. However, little is known about the relationship between dietary components and AAA. In this study, we estimated the effect of dietary deoxyribonucleic acid (DNA) on the vascular wall. After habituation for 5 d, the mice were divided into four groups: control diet and distilled water group (C), DNA-Na diet and distilled water group (DNA), control diet and 0.5 mg/mL nicotine solution group (C-Nic), DNA-Na diet, and 0.5 mg/mL nicotine solution group (DNA-Nic). The dietary DNA attenuated the degradation of elastin fibers induced by nicotine administration. The areas stained positive for MMP-2 in the DNA-Nic group were significantly suppressed compared to C-Nic mice. These data suggest that the dietary DNA may prevent the weakening of the aortic wall via inhibition of the MMP-2-dependent pathway. In conclusion, we have revealed the protective effect of dietary DNA on the vascular pathology of nicotine-administrated mice. A nucleic acid-rich diet might be useful for people who consume nicotine via smoking, chewing tobacco, or nicotine patches.

Role of Vitamin D in Uremic Vascular Calcification.

The risk of cardiovascular death is 10 times higher in patients with CKD (chronic kidney disease) than in those without CKD. Vascular calcification, common in patients with CKD, is a predictor of cardiovascular mortality. Vitamin D deficiency, another complication of CKD, is associated with vascular calcification in patients with CKD. GFR decline, proteinuria, tubulointerstitial injury, and the therapeutic dose of active form vitamin D aggravate vitamin D deficiency and reduce its pleiotropic effect on the cardiovascular system. Vitamin D supplement for CKD patients provides a protective role in vascular calcification on the endothelium by (1) renin-angiotensin-aldosterone system inactivation, (2) alleviating insulin resistance, (3) reduction of cholesterol and inhibition of foam cell and cholesterol efflux in macrophages, and (4) modulating vascular regeneration. For the arterial calcification, vitamin D supplement provides adjunctive role in regressing proteinuria, reverse renal osteodystrophy, and restoring calcification inhibitors. Recently, adventitial progenitor cell has been linked to be involved in the vascular calcification. Vitamin D may provide a role in modulating adventitial progenitor cells. In summary, vitamin D supplement may provide an ancillary role for ameliorating uremic vascular calcification.

Effects of tongxinluo on angiogenesis in the carotid adventitia of hyperlipidemic rabbits.

Atherosclerosis, as a common arterial disease with high morbidity rate, is reported to be closely associated with adventitia angiogenesis. The present study aimed to investigate the effect of tongxinluo (TXL) on angiogenesis in the carotid adventitia of hyperlipidemic rabbits and the underlying mechanism. A total of 90 experimental rabbits were randomly assigned into the following six groups (n=15 per group): Normal group, model group, low­dose TXL group, moderate-dose TXL group, high­dose TXL group and atorvastatin group. The normal group was fed with a standard diet. The model and treatment groups were on a high cholesterol diet for 4 weeks. The serum lipid level of the model group was significantly higher compared with the normal group. TXL serum lipid level compared with the model group. Hematoxylin and eosin, and CD31 staining demonstrated that TXL inhibited adventitia angiogenesis in a dose­dependent manner. The dihydroethidium probe and fluorescence in situ hybridization results indicated that TXL reduced O2­ level and positive signal of gp91phox and p22phox mRNA in adventitia. Reverse transcription­polymerase chain reaction and western blot analysis determined that TXL treatment significantly downregulated the expression levels of the gp91phox, p22phox genes and the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) proteins compared with the model group. TXL exhibited a dose­dependent inhibitory effect on angiogenesis in the carotid adventitia of hyperlipidemic rabbits. This may be associated with the downregulation of reactive oxygen species generation in the adventitia and the suppression of VEGF/VEGFR-2 expression.

Qindan capsule changes adventitial collagen synthesis in spontaneously hypertensive rats.

OBJECTIVE: To investigate the effect of Qindan capsule (QC) on collagen synthesis and the mechanism underlying the process in spontaneously hypertensive rats (SHRs). METHODS: Twentyfour SHRs were divided into three groups: the hypertension model group, the QC treatment group, and the losartan treatment group. Eight Wistar Kyoto (WKY) rats were used as the normal control group. The systolic blood pressure (SBP) of the rats was monitored, and the thoracic aorta adventitia of the rats was segregated. The expressions of transforming growth factor 1 (TGF-ß1), Smad3, and collagens I and were measured by histological staining and reverse transcription polymerase chain reaction. RESULTS: The SBP was significantly higher in the model group than in the normal control group (P<0.01). However, a significant SBP-lowering effect was observed in QC or losartan treatment groups (P<0.05 or P<0.01) after 3 weeks of treatment. QC-treated rats showed a decrease of approximately 40 mm Hg, and the losartan-treated rats showed a decrease of approximately 50 mm Hg at the end of treatment compared with the beginning of treatment. The protein and gene levels of TGF-ß1, Smad3, and collagens I and in the model group were significantly increased compared with those in the normal control group (P<0.01). However, the levels were significantly decreased in the QC or losartan treatment group compared with the model group (P<0.05 or P<0.01). However, there was no significant difference between the QC and losartan treatment groups (P<0.05). CONCLUSIONS: QC could exert its antihypertensive effect through down-regulating TGF-ß1-stimulated collagen expressions. The TGF-ß1/Smad3 signaling pathway may be involved in this process.

[Effect of adventitia cells on occurrence and development of atherosclerosis].

The effect of adventitia on the occurrence and development of atherosclerosis (As) is getting more attentions. Fibroblasts, mast cells, dendritic cells, vasa vasorums, vascular-associated lymphoid tissues, and vascular peripheral nerves are related to the occurrence and development of As. This essay summarizes studies on the changes in adventitia in As process and its effect on the occurrence and development of As, as well as the latest progress.

Low level laser arrests abdominal aortic aneurysm by collagen matrix reinforcement in apolipoprotein E-deficient mice.

BACKGROUND AND OBJECTIVES: Recent in vitro studies by our group indicated that low level laser irradiation (LLLI) modifies cellular processes essential to the progression of abdominal aortic aneurysm (AAA). Using high-frequency ultrasonography (HF-u/s) in the angiotensin-II (Ang-II)-infused, apolipoprotein-E-deficient (Apo-E(-/-) ) mouse model of AAA, we found that LLLI markedly inhibited aneurysm formation and preserved arterial wall elasticity. We now report, using quantitative histopathology, the likely mechanism underlying the preventative effect of LLLI on aneurysm formation in this model. STUDY DESIGN/MATERIALS AND METHODS: This study was performed on 32 Apo-E(-/-) mice of which 10 were Ang-II-infused and LLL-irradiated (780 nm, 2 J/cm(2) , 9-minutes), 12 were Ang-II-infused but not irradiated, and 10 were saline infused. The aortas were excised at 28d, sectioned at 250 µm intervals, and stained with H + E, Movat-pentachrome and picrosirius-red for histomorphometry, and immunostained with Mac-2 and α-actin for detection of macrophages and SMCs, respectively. RESULTS: Transmural disruptions of the aorta occurred with distinct predilection for branch orifices. In the LLLI-treated animals, the frequency of these disruptions was lower (#branches with break points: 17 of 40 vs. 32 of 48, P = 0.023 by Chi-squared), their size smaller (length [mm]: 0.48 ± 0.26 vs. 0.98 ± 1.42, P = 0.044 by ANOVA with FPLSD), and the number of Mac-2-positive macrophages in the intramural areas of these disruptions lower than in the non-treated control (#Macrophages/0.01 mm(2) at break points: 11.6 ± 7.2 vs. 26.0 ± 15.7, P = 0.016 by Kruskal-Wallis). The average size of the medial SMCs was larger reflecting a heightened synthetic state (SMC size [µm(2) ]: 463.9 ± 61.4 vs. 354.9 ± 71.7, P = 0.001 by ANOVA with FPLSD). Furthermore, at sites of transmural disruption, the %area occupied by collagen of the overall area of attempted repair (%Col/WO) was significantly greater in the LLLI-treated animals versus control (%Col/WO: 41 ± 13 vs. 32 ± 16, P = 0.009 by ANOVA with FPLSD). CONCLUSION: Enhanced matrix reinforcement and modification of the inflammatory response at sites of transmural injury are prominent mechanisms by which LLLI reduces AAA progression in this model.