Renovascular hypertension: screening and modern management

The diagnosis and management of patients with renovascular disease and hypertension continue to elude healthcare providers. The advent of novel imaging and interventional techniques, and increased understanding of the pathways leading to irreversible renal injury and renovascular hypertension, have ushered in commendable attempts to optimize and finetune strategies to preserve or restore renal function and control blood pressure. Large randomized clinical trials that compare different forms of therapy, and smaller trials that test novel experimental treatments, will hopefully help formulate innovative concepts and tools to manage the patient population with atherosclerotic renovascular diseas

Potential Role of the Ubiquitin-Proteasome System in Atherosclerosis Aspects of a Protein Quality Disease

Misfolded or damaged proteins are recognized intracellularly by protein quality mechanisms. These include chaperones and the ubiquitin-proteasome system, which aim at restoration of protein function and protein removal, respectively. A number of studies have outlined the functional significance of the ubiquitin-proteasome system for the heart and, as of recently, for the vascular system. This review summarizes these recent findings with a focus on atherosclerosis. In particular, this paper reflects on the viewpoint of atherosclerosis as a protein quality disease

Endothelial dysfunction over the course of coronary artery disease

The vascular endothelium regulates blood flow in response to physiological needs. Endothelial dysfunction is closely related to atherosclerosis and its risk factors, and it constitutes an intermediate step on the progression to adverse events throughout the natural history of coronary artery disease (CAD), often affecting clinical outcomes. Understanding the relation of endothelial function with CAD provides an important pathophysiological insight, which can be useful both in clinical and research management. In this review, we summarize the current knowledge on endothelial dysfunction and its prognostic influence throughout the natural history of CAD, from early atherosclerosis to post-transplant managemen

Endothelial dysfunction over the course of coronary artery disease

The vascular endothelium regulates blood flow in response to physiological needs. Endothelial dysfunction is closely related to atherosclerosis and its risk factors, and it constitutes an intermediate step on the progression to adverse events throughout the natural history of coronary artery disease (CAD), often affecting clinical outcomes. Understanding the relation of endothelial function with CAD provides an important pathophysiological insight, which can be useful both in clinical and research management. In this review, we summarize the current knowledge on endothelial dysfunction and its prognostic influence throughout the natural history of CAD, from early atherosclerosis to post-transplant managemen

Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering

AbstractObjectivesThis study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia.BackgroundSimvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown.MethodsPigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated.ResultsTotal and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05).ConclusionsThese findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering

Patients with Carotid Intraplaque Hemorrhage Have Higher Incidence of Cerebral Microbleeds

Aims: Carotid intraplaque hemorrhage (IPH) is considered a marker of plaque vulnerability. Cerebral microbleeds (CMBs) are recognized on magnetic resonance imaging (MRI) in patients with cerebrovascular disease. Any connection between carotid IPH and CMBs remains scantly investigated. This study aimed to determine whether the histologic evidence of carotid IPH is related to CMBs. Methods: We retrospectively enrolled 101 consecutive patients undergoing carotid endarterectomy with symptomatic (ischemic stroke, TIA, and amaurosis fugax) or asymptomatic ipsilateral carotid artery disease. The presence and the extent (%) of IPH were identified on carotid plaques stained with Movat Pentachrome. CMBs were localized on T2*-weighted gradient-recalled echo or susceptibility-weighted imaging sequence on brain MRI before surgery. The degree of carotid stenosis was measured by neck CTA. Results: IPH was identified in 57 (56.4%) patients, and CMBs were found in 24 (23.7%) patients. CMBs were more commonly observed in patients with carotid IPH compared to those without [19 (33.3%) vs 5 (11.4%); P=0.010]. The carotid IPH extent was significantly higher in patients with CMBs than in those without [9.0 % (2.8-27.1%) vs 0.9% (0.0-13.9%); P=0.004] and was associated with the number of CMBs (P=0.004). Logistic regression analysis demonstrated an independent association between carotid IPH extent and the presence of CMBs [OR 1.051 (95% CI 1.012-1.090); P=0.009]. Additionally, patients with CMBs had a lower degree of ipsilateral carotid stenosis compared to those without [40% (35-65%) vs 70% (50-80%); P=0.049]. Conclusions: CMBs may be potential markers of the ongoing process of carotid IPH, especially in those with nonobstructive plaques

Endothelin-1 receptor blockade prevents renal injury in experimental hypercholesterolemia

Endothelin-1 receptor blockade prevents renal injury in experimental hypercholesterolemia.BackgroundThe potent vasoconstrictor endothelin-1 is involved in regulation of renal function, and is up-regulated in hypercholesterolemia (HC), a risk factor for renal disease that increases oxidative stress and impairs renal hemodynamic responses. However, the involvement of endothelin (ET) in this disease process is yet unknown.MethodsRegional renal hemodynamics and function in vivo were quantified in pigs at baseline and during infusion of acetylcholine using electron beam computed tomography after a 12-week normal diet (N = 6), HC diet (N = 6), and HC diet orally supplemented (4mg/kg/day) with the selective ET receptor-A (ET-A) blocker ABT-627 (HC+ET-A, N = 6). Plasma levels of 8-epi-PGF2-α-isoprostanes, markers of oxidative stress, were measured using enzyme immunoassay, and renal tissue was studied ex vivo using Western blotting, electrophoretic mobility shift assay, and immunohistochemistry.ResultsTotal and low-density lipoprotein (LDL) cholesterol were similarly increased, but isoprostanes were decreased in HC+ET-A compared to HC alone. Basal renal perfusion was similar among the groups, while glomerular filtration rate (GFR) increased in HC+ET-A compared to HC. Stimulated perfusion and GFR were blunted in HC, but normalized in HC+ET-A. Moreover, ET blockade increased expression of endothelial nitric oxide synthase, and decreased endothelial expression of the oxidized-LDL receptor LOX-1, as well as tubular immunoreactivity of inducible nitric oxide synthase, nitrotyrosine, nuclear factor-κB, transforming growth factor-β, and tubulointerstitial and perivascular trichrome staining.ConclusionET-A blockade improves renal hemodynamic and function in HC, and decreases oxidative stress, and renal vascular and tubulointerstitial inflammation and fibrosis. These findings support a role for the endogenous ET system in renal injury in HC and atherosclerosis