These results led us to propose AF as a new possible pathophysiological link between arterial stiffness and stroke. These results also emphasize the cardiac consequences of arterial stiffness which can fuel a new approach to AF prevention.

Graft-prosthesis and stentgraft placements are effective modalities for treating abdominal aortic aneurysm, but related changes in arterial stiffness are not well established. The present study sought to assess aortic stiffness after aneurism repair by measuring pulse wave velocity (PWV). The graft-related variation of carotid-femoral PWV was compared with that of carotid-radial PWV, the latter being unaffected by vascular treatment. The secondary objective was to evaluate potential differences between graft-prosthesis and stentgraft in terms of aortic stiffness and augmentation index, a composite indicator integrating wave reflexion. Fifty patients were included (39 had a graft-prosthesis and 11 had a stentgraft). In the whole group and after a median postoperative follow-up of 47 days, carotid-femoral PWV increased by +1.0 m/s [-12.3, +10.3], while carotid-radial PWV slightly decreased by -0.3 m/s [-4.4; +3.5] (P = 0.001). The effect of the type of prosthesis on the PWV was not significant. Nevertheless, the augmentation index increased after stentgraft implantation (+4% [-10; +17]) and decreased after graft-prosthesis placement (-8.5% [-47; +17]) (P < 0.01). This difference was not explained by a heart rate or a treatment effect and was likely attributable to the prosthesis per se. This study demonstrates the impact of aortic grafts on aortic stiffness. Besides, it suggests that stentgraft increases reflected waves more than graft-prostheses. These changes of vascular properties may influence the outcomes after surgery.

Abstract-Natriuretic peptides are controregulatory hormones associated with cardiac remodeling, namely, left ventricular hypertrophy and systolic/diastolic dysfunction. We intended to address the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in hypertension. We prospectively studied the relationship between plasma NTproBNP and all-cause mortality in 684 hypertensive patients with no history or symptoms of heart failure referred for hypertension workup in our institution from 1998 to 2008. After a mean duration of 5.7 years, we observed 40 deaths (1.04 deaths per 100 patients per year). After adjustment for traditional cardiovascular risk factors, including ambulatory blood pressure and serum creatinine, the risk for all-cause mortality more than doubled with each increment of 1 log NT-proBNP (hazard ratio: 2.33 [95% CI: 1.36 to 3.96]). The risk of death of patients with plasma NT-proBNP Ն133 pg/mL (third tertile of the distribution) was 3.3 times that of patients with values Ͻ50.8 pg/mL (first tertile; hazard ratio: 3.30 [95% CI: 0.90 to 12.29]). This predictive value was independent of, and superior to, that of 2 ECG indexes of left ventricular hypertrophy, the Sokolov-Lyon index and the amplitude of the R wave in lead aVL. In addition, it persisted in patients without ECG left ventricular hypertrophy, which allowed refining risk stratification in this relatively low-risk patient category. In this large sample of hypertensive patients, plasma NT-proBNP appeared as a strong prognostic marker. This performance, together with the ease of measurement, low cost, and widespread availability of NT-proBNP test kits, should prompt a wide use of this marker for risk stratification in hypertension. (Hypertension. 2011;57:702-709.)Key Words: hypertension Ⅲ NT-proBNP Ⅲ survival Ⅲ risk stratification Ⅲ left ventricular hypertrophy I n hypertension, detection of cardiac damages is critical for risk stratification. 1 This is usually done by searching for left ventricular hypertrophy (LVH), a major predictor of cardiovascular events. 2,3 However, in clinical practice, LVH detection is subject to various limitations. ECG is recommended by most guidelines but has a poor sensitivity and is rarely performed in clinical practice. 4 Echocardiography is extensively used but is time consuming, expensive, and not always feasible for technical reasons. The cost-effectiveness of its systematic use in hypertensive patients is still widely debated. 5 Thus, there is still room for new cardiac markers to be used for risk stratification.In response to volume expansion and pressure load, ventricular myocytes release a cardiac hormone, the B-type natriuretic peptide (BNP), together with its amino-terminal fragment, the N-terminal proBNP (NT-proBNP). 6 BNP and NT-proBNP are strong prognostic markers in advanced stages of cardiac diseases like heart failure 7 or coronary disease. 8 They are also closely related to cardiac geometry and mass, 9 and we have recently demonstrated the good performance of plasma NTproBNP for t...

All components required for angiotensin II formation are expressed locally in the arterial wall, where, in the absence of renin, cathepsin G could be a major angiotensin-generating enzyme. Overexpression of ACE and cathepsin G may lead to angiotensin II overproduction and contribute, with decreased number of differentiated smooth muscle cells, to the lower amount of AT1 receptor in atheroma.

Objective-Because inhibition of the renin-angiotensin system (RAS) reduces the onset of type 2 diabetes (T2D) and prevents atherosclerosis, we investigated the expression of RAS in the arterial wall of T2D and nondiabetic (CTR) patients. Methods and Results-mRNA and protein levels of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AT1 receptor (AT1R) were determined in carotid atheroma plaque, nearby macroscopically intact tissue (MIT), and in vascular smooth muscle cells (VSMCs) before and after insulin stimulation from 21 T2D and 22 CTR patients. AGT and ACE mRNA and their protein levels were 2-to 3-fold higher in atheroma and in MIT of T2D patients. VSMCs from T2D patients had respectively 2.5-and 5-fold higher AGT and AT1R mRNA and protein contents. Insulin induced an increase in AGT and AT1R mRNA with similar ED50. These responses were blocked by PD98059, an inhibitor of MAP-kinase in the two groups whereas wortmannin, an inhibitor of PI3-kinase, partially prevented the response in CTR patients. Phosphorylated ERK1-2 was 4-fold higher in MIT from T2D than from CTR patients. Conclusions-The arterial RAS is upregulated in T2D patients, which can be partly explained by an hyperactivation of the ERK1-2 pathway by insulin. Key Words: renin Ⅲ carotid atheroma Ⅲ type 2 diabetes mellitus Ⅲ MAP-kinase Ⅲ P85-PI3-kinase T ype 2 diabetes mellitus (T2D) is an important risk factor of atherosclerosis, and nearly 80% of diabetic patients die of cardiovascular disease. 1 The inhibition of the renin-angiotensin system (RAS) may be achieved with angiotensin converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT1R) antagonists. These drugs demonstrated a decrease in the mortality and frequency of cardiovascular events, in primary prevention of cardiovascular diseases in high risk patients (Heart Outcomes Prevention Evaluation study [HOPE], Losartan Investigation For Endpoints reduction in hypertension study [LIFE]) and in secondary prevention after myocardial infarction (Gruppo Italiano per lo Studio della Soppravvivenza nell'Infarto miocardico [GISSI3], International Study of Infarct Survival-4 [ISIS4]). [2][3][4] In atherosclerotic regions of arteries, the amounts of immunoreactive ACE and angiotensin II (Ang II) are significantly increased. [5][6][7][8] We previously showed that ACE and other enzymes such as cathepsin G and tissue kallikrein that are able to cleave Ang II from AGT mRNA were also increased in carotid atheroma with a concomitant decrease in AT1R mRNA. 9,10 This suggests that RAS is involved in the atherogenic process. Inhibition of RAS in T2D patients has been shown to be more beneficial than in nondiabetic subjects in terms of reduction of cardiovascular events. 1,2 Moreover, RAS blockers reduced the development of diabetes and insulin resistance in hypertensive patients. 2,11 Thus, RAS is likely to be involved in the development of both insulin resistance and atheroma.Insulin has been shown to activate, via the MAP kinase ERK1-2 pathway, the expression of AGT and AT1R in vascu...

Objective-Accumulation of cholesterol in foam cells of atheroma plaques depends on the balance between uptake and efflux of cholesterol. It may also depend on proteins surrounding lipid droplets, adipophilin, and perilipins. They favor triglyceride storage in adipocytes and could play a similar role for cholesterol in atheroma. Methods and Results-We measured in human atheroma and nearby macroscopically intact tissue (MIT) the expression of perilipin, adipophilin, and regulatory factors of cholesterol metabolism. We identified perilipin A in human arterial wall. Its expression was largely increased in atheroma compared with MIT, and perilipin was present in macrophages and vascular smooth muscle cells. Adipophilin, ACAT1, and CD36 were also overexpressed in atheroma. mRNA levels of low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and SREBP-2 were unchanged. With respect to efflux of cholesterol, the mRNA levels of NCEH and ABCA-1 were unchanged, whereas CLA-1 mRNA was slightly higher in atheroma. Importantly, immunoblotting of ABCA-1 showed a dramatic decrease of ABCA1 protein, the key molecule of cholesterol efflux, in atheroma compared with MIT. Conclusion-We

In the present study, UAGT stands as a strong predictor of BP in women with low plasma renin/aldosterone, suggesting an involvement of the tubular renin-angiotensin system in these subjects. Higher sodium intake or the need to maintain treatment may account in part for the lack of a similar relationship in males.

Objective-Cholesterol accumulation in macrophages is known to alter macrophage biology. In this article we studied the impact of macrophage cholesterol loading on gene expression and identified a novel gene implicated in cell death. Methods and Results-The regulated in development and DNA damage response 2 (REDD2) gene was strongly upregulated as THP-1 macrophages are converted to foam cells. These results were confirmed by Northern blot of RNA from human monocyte-derived macrophages (HMDM) treated with oxidized LDL (oxLDL). Human REDD2 shares 86% amino acid sequence identity with murine RTP801-like protein, which is 33% identical to RTP801, a hypoxia-inducible factor 1-responsive gene involved in apoptosis. Treatment of HMDM with desferrioxamine, a molecule that mimics the effect of hypoxia, increased expression of REDD2 in a concentration-dependent fashion. Transfection of U-937 and HMEC cells with a REDD2 expression vector increased the sensitivity of the cells for oxLDL-induced cytotoxicity, by inducing a shift from apoptosis toward necrosis. In contrast, suppression of mRNA expression using siRNA approach resulted in increased resistance to oxLDL treatment. Key Words: REDD2 Ⅲ macrophages Ⅲ atherosclerosis Ⅲ hypoxia Ⅲ oxLDL Ⅲ necrosis Ⅲ apoptosis I t is well-established that elevation of plasma low-density lipoproteins (LDL) is a risk factor for atherosclerosis, and that lesion-prone areas show increased intramural retention of lipoproteins by the extracellular matrix. 1 Many of these lipoproteins are modified mainly through glycation, aggregation, protease degradation, and oxidation and as such become increasingly atherogenic. 2,3 Several studies have indicated that a diversity of effects on macrophage function can be attributed to modified LDL. These include growth stimulation, 4 -6 proinflammatory effects such as expression of inflammatory cytokines, 7 increase in cytotoxicity 8 and in expression of metalloproteinases, inhibition of expression of inducible nitric oxide synthase, 9,10 and effects on lipid metabolism and accumulation. [11][12][13] The human leukemia cell line THP-1 has been used as a model for the monocyte-macrophage lineage. 14 On treatment with phorbol esters, these cells take on the characteristics of activated macrophages, including decreased LDL receptor expression and increased expression of scavenger receptors. These changes in gene expression enable the cells to take-up modified lipoproteins and subsequently to develop a foam cell-like morphology. Using a powerful DNA microarray approach, Shiffman et al 15 have identified several upregulated genes in THP-1 cells loaded with oxidized LDL (oxLDL). In addition, Yuchang et al have also reported several differentially expressed genes in oxLDL-treated compared with nontreated THP-1 cells using the subtractive approach. 16 In this study, we have combined the subtractive and the DNA microarray approaches and identified additional genes induced in cholesterol loaded THP-1 macrophages. Among the most significant upregulated genes, one express...