In patients with a first episode of acute symptomatic PE, the presence of concomitant DVT is an independent predictor of death in the ensuing 3 months after diagnosis. Assessment of the thrombotic burden should assist with risk stratification of patients with acute PE.

Results: ILK expression was detected in the endothelial cell layer of nonatherosclerotic vessels but was absent from the endothelium of atherosclerotic arteries. Live ultrasound imaging revealed that acetylcholine-mediated vasodilatation was impaired in cKO mice. These mice exhibited lowered agonist-induced nitric oxide synthase (NOS) activity and decreased cyclic guanosine monophosphate and nitrite production. ILK deletion caused endothelial NOS (eNOS) uncoupling, reflected in reduced tetrahydrobiopterin (BH4) levels, increased BH2 levels, decreased dihydrofolate reductase expression, and increased eNOS-dependent generation of superoxide accompanied by extensive vascular protein nitration. ILK reexpression prevented eNOS uncoupling in cKO cells, whereas superoxide formation was unaffected by ILK depletion in eNOS-KO cells, indicating eNOS as a primary source of superoxide anion. eNOS and ILK coimmunoprecipitated in aortic lysates from control animals, and eNOS-ILK-shock protein 90 interaction was detected in human normal mammary arteries but was absent from human atherosclerotic carotid arteries. eNOS-ILK interaction in endothelial cells was prevented by geldanamycin, suggesting heat shock protein 90 as a binding partner. Key Words: atherosclerosis Ⅲ oxidative stress Ⅲ uncoupling protein E ndothelial dysfunction is defined as impaired endothelium-dependent relaxation of blood vessels in response to the endogenous vasodilator nitric oxide (NO). Endothelial dysfunction is concomitant with changes in vascular structure associated with many forms of vascular disease, such as hypertension and atherosclerosis. 1 Atherosclerotic lesions develop mostly in areas exposed to disturbed blood flow, whereas endothelial cells exposed to laminar flow are protected against inflammatory activation and show higher relative expression of endothelial NO synthase (eNOS) and superoxide dismutase. 2,3 Most NO in the vasculature is produced by eNOS, with a minor contribution from neuronal-type nNOS expressed in vascular smooth muscle cells. Under inflammatory conditions, vascular cells can express iNOS, which produces large amounts of NO and contributes further to vascular damage. 4 eNOS can be activated by hemodynamic forces, autacoids, hormones, and growth factors. NO relaxes vessels via activation of soluble guanylyl cyclase (sGC). The resulting elevated levels of cyclic guanosine monophosphate (cGMP) activate cGMP-dependent protein kinase type I (cGKI), which phosphorylates downstream targets that regulate the Original received July 29, 2011; revision received December 13, 2011; accepted December 14, 2011. In November 2011 actin-myosin cytoskeleton and the calcium clearing mechanism, leading to vasorelaxation. 5 Many endothelial cell molecules, including integrins, sense shear stress. 6,7 Integrin-linked kinase (ILK), a key regulator of blood vessel integrity, is a phosphoinositide 3-kinasedependent serine/threonine kinase that binds to the cytoplasmic domain of ß-integrin and lies upstream of many intracellular signaling pa...

Nitric Oxide (NO) is involved in the development and progression of abdominal aortic aneurysms (AAA).We found that inhibition of inducible NO synthase (iNOS) protects mice in an elastase-induced AAA model, significantly inhibiting the production of matrix metalloproteinase-13 (MMP-13). The extracellular MMP inducer (EMMPRIN; CD147) was increased in human AAA biopsies and in wild-type murine AAA but not in AAA from iNOS null mice. In cells overexpressing ectopic EMMPRIN, MMP-13 secretion was stimulated, whereas silencing of EMMPRIN by RNA interference led to significant inhibition of MMP-13 expression. In addition, elastase infusion of MMP-13 null mouse aortas induced a significant increase of EMMPRIN but reduced aortic dilatation when compared with wildtype mice, suggesting that NO-mediated AAA may be mediated through EMMPRIN induction of MMP-13. These findings were further verified in elastase-infused iNOS null mice, in which daily administration of NO caused a significant aortic dilatation and the expression of EMMPRIN and MMP-13. By contrast, in iNOS wild-type mice, pharmacological inhibition of iNOS by administration of 1400 W induced a reduction of aortic diameter and inhibition of MMP-13 and EMMPRIN expression when compared with control mice. Our results suggest that NO may regulate the development of AAA in part by inducing the expression of EMMPRIN and modulating the activity of MMP-13 in murine and human aneurysms. Abdominal aortic aneurysm (AAA) is an age-related multifactorial cardiovascular disease and is usually asymptomatic until rupture or diameter size requires medical intervention. 1,2AAA is characterized by local chronic inflammation, degradation of the medial elastin, and components of the extracellular matrix. Resistance to rupture depends on tensile strength by interstitial collagens, and therefore, collagen-degrading enzymes may play a pivotal effect. 3Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes involved in the development and progression of AAA in humans and mice. The effect of collagenases MMP-8 3 and MMP-13, 4 gelatinases A and B, 5 and membrane type MMPs 6 have been extensively analyzed. In particular, collagenases are responsible of cleavage of type I and III collagens, which are involved in keeping the vessel tensile strength, and therefore, increased production of collagen-degrading enzymes may be determinant for the progression of AAA. However, the molecular mechanisms leading to MMP expression and activation are not fully understood.The expression of MMPs have been recently associated to cardiovascular disease through the activation of the extracellular MMP inducer (EMMPRIN; Basigin and CD147).7 EMMPRIN is an immunoglobulin, which induces the expression of MMP-2, MMP-9, and MT1-MMP. 8 -13 Acute and chronic inflammation induces the expression of EMMPRIN by immune cells and vascular endothelial cells, and its role on MMP expression was related to atherosclerosis. 14,15Here we show the association of EMMPRIN and MMP-13 in human AAA and during the NO-me...

BackgroundThe beneficial effects in lipid profiles after obesity surgery might be associated with the decrease in cardiovascular risk. However, direct comparison between different surgical techniques has not been extensively performed.MethodsIn the present study we compare 20 obese women submitted to laparoscopic Roux en Y gastric bypass (RYGB) with 20 women submitted to sleeve gastrectomy (SG). Twenty control women matched for age and baseline cardiovascular risk were also included. Both patients and controls were followed up for 1 year after surgery or conventional treatment with diet and exercise, respectively. Lipid profiles were measured at baseline, 6 and 12 months later. Carotid intima-media thickness was measured by ultrasonography at baseline and at the end of the study.ResultsWomen submitted to bariatric surgery showed a decrease in total cholesterol, triglycerides, oxidized-LDL and ApoB, and an increase in HDL and ApoA concentrations that occurred regardless of the surgical procedure. LDL concentrations, however, decreased only after RYGB whereas Lp(a) showed no changes. We did not observe any correlation between the changes in serum lipid concentrations and those in carotid intima-media thickness.ConclusionsSleeve gastrectomy and gastric bypass induce a similar beneficial effect on serum lipids in women with high cardiovascular risk 1 year after surgery.