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Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,666 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10−14, 5.3 x 10−9 and 8.8 x 10−8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

Pulmonary vascular reactivity is thought to be greater in the newborn than adult lung. To determine the influence of the endothelium on smooth muscle cell contractility, responses of rings of isolated intrapulmonary arteries were studied from pigs at birth aged <2 h, 2 d, 3 d, and 10 d (n = 4 per age group) and from eight adult animals. At birth, the response to KC1 (25 mM) and prostaglandin F,, (PGF,,) (3 pM) but not histamine (0.1 mM) was greater in rings with endothelium (E+) than without (E-). The response to PGF,, decreased between birth and 3 d by which time the contraction was less in E+ rings than E-, but L-nitro monomethyl arginine augmented contraction at all ages. In the immature piglets, the response to phenylephrine was less in E+ rings than E-, an effect which was reversed by L-Nwnitro-L-arginine methyl ester. The response to all contractile agonists increased between 10 d and adulthood. The concentration of plasma endothelin-1 was determined in all animals by RIA and was higher at birth than at 3 d or later. In summary, I ) at birth, endothelium enhanced contractility, when plasma endothelin was greatest, but released NO in the presence of phenylephrine and PGF,,; 2) contractile response to all agonists was small at birth; and 3) a complex interaction existed between the contractile agonist and the effect of endothelial maturation. This study suggests that excessive reactivity in the newborn pulmonary vasculature may be due to immaturity of mechanisms determining endothelium-dependent arterial relaxation, but not to an excessive contractile response. (Pediatr Res 38: [25][26][27][28][29]1995) Abbreviations PGF,,, prostaglandin F, , PE, phenylephrine L-NAME, N"-nitro-L-arginine methyl ester L-NMMA, L-nitro monomethyl arginine EDRF, endothelium-derived relaxing factor NO, nitric oxide At birth, the pulmonary arterial pressure and resistance are high and decrease rapidly during the first hours after birth due to structural (1-3) and functional (4, 5) remodeling. The mechanisms responsible for these changes are not fully elucidated, but EDRF is known to play a role. EDRF (6-8) is released from the lungs of fetal and newborn animals (9-11).It helps reduce basal tone in utero and contributes to the postnatal fall in pulmonary vascular resistance. However, endothelium-dependent relaxation to acetylcholine is absent at birth in the porcine lung and does not appear until the third day of life (5). In the ovine lung, endothelial-dependent relaxation in response to acetylcholine, ADP, and calcium ionophore (A23187) is minimal in utero and at birth and increases rapidly during the first week of life (12). These observations suggest that immediately after birth the interactions between the endothelium and the underlying smooth muscle may be different from those in adult porcine pulmonary vasculature. In mature blood vessels, the endothelium is thought to play an important role in the control of vascular tone through a balance between EDRF such as NO (lo), prostacyclin (13), bradykinin (14), the endothelium-...

Plasma adiponectin could be indicative of mortality after a bypass operation for patients with advanced peripheral arterial disease.

Aim:To assess the utility of skin perfusion pressure (SPP) measurement in evaluating the outcome of vascular constructions for critical limb ischemia (CLI) patients. Methods: We retrospectively studied 19 lower limbs in 18 patients who underwent arterial reconstruction for CLI from whom SPP measurements had been obtained pre-and postoperatively between 2008 and 2010. Six limbs whose ulcers had healed postoperatively were classified into group H, 7 limbs whose ulcers had not healed into group U, and 6 limbs without ulcers into group N. SPP values were compared among these groups. Results: The preoperative SPP values in all groups were <30 mmHg, without significant differences among the groups. The SPP values in groups H and N significantly improved after operation, and those in group U were significantly lower than those in the other groups. Conclusions: SPP measurement before and after arterial reconstruction is useful to assess improvement in tissue circulation and to predict the likelihood of wound healing. An SPP value ≥30 mmHg was considered necessary for wound healing, supporting the findings of the few reports in the literature on the usefulness of SPP for assessing vascular reconstruction effects on ulcer wound healing.

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A flow-mediated endothelium-dependent vasodilation and endothelium-independent nitroglycerin-induced vasodilation were carried out in 70 patients and 15 age-matched adults without any atherosclerotic risk factors to clarify vascular responsiveness in patients with atherosclerotic peripheral vascular disease. The percent change in flow-mediated vasodilation was significantly lower in patients than in controls (5.4 +/- 0.7% vs 12.8 +/- 2.2%, P < .001). Moreover, the percent change in nitroglycerin-induced vasodilation measured after sublingual administration of nitroglycerin was lower in patients than in controls (5.8 +/- 0.6% vs 10.2 +/- 1.5%, P < .01). On multiple regression analysis, none of the determinant factors showed a significant correlation with flow-mediated vasodilation. In contrast, Fontaine classification was found to be a significant predictor for nitroglycerin-induced vasodilation (r = -0.307, P < .05). There is a significant positive correlation between nitroglycerin-induced vasodilation and ankle-brachial pressure index in the patients. The data showed that vasoditation function were markedly impaired in end-stage patients with peripheral vascular disease.

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