Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent data support a modulatory role for CD4 T cells in experimental renal ischemia-reperfusion injury (IRI). CD4 T cells can functionally differentiate to either a Th1 (IFN-gamma producing) or the counterbalancing Th2 (IL-4) phenotype. The enzymes signal transducers and activators of transcription (STAT) 4 and STAT6 regulate Th1 or Th2 differentiation and cytokine production, respectively. We therefore hypothesized that mice that were STAT4 deficient would be protected from renal IRI and that STAT6-deficient mice would have a more severe course. Intracellular cytokine staining of splenocytes from STAT4-/- or STAT6-/- exhibited distinct IFN-gamma and IL-4 cytokine expression profiles. STAT6-/- had markedly worse renal function and tubular injury postischemia compared with wild type. STAT4-/- had only mildly improved function. Renal phagocyte infiltration and ICAM-1 upregulation were similar in STAT4-/-, STAT6-/-, and wild type. To evaluate if the mechanism of the marked worsening in the STAT6-/- mice could be due to IL-4 deficiency, IL-4-deficient mice were studied and had similar postischemic phenotype to STAT6-/- mice. These data demonstrate that the STAT6 pathway has a major protective role in renal IRI. IL-4 deficiency is a likely mechanism underlying the STAT6 effect. A "yin-yang" role for inflammation is emerging in renal IRI, similar to recent observations in atherosclerosis.
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PMID:Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury. 1270 97

Cholesterol crystal embolization (CCE) is a dreaded complication of radiology, vascular surgery, and/or anticoagulation in patients with atherosclerosis and ulcerated aortic plaques. It also represents a cause of early graft failure and of poor results of renal artery surgery. Crystals lodge in small caliber renal arteries, where they induce early, transitory thrombosis followed by delayed, definitive obstruction by endarteritis, accompanied by evidence of inflammation and eosinophilia. Massive CCE leads to early oligoanuria. In subacute forms, renal insufficiency is often delayed by weeks or months following the triggering event. A third, chronic subset of CCE is easily mistaken for atherosclerotic renal ischemia and/or nephrosclerosis. The kidney is rarely the sole organ involved in acute/subacute forms, in which the central nervous system, the coronary arteries, the spinal cord, and the mesenteric and pancreatic blood supply compromise represent the main causes of death. Cutaneous, retinal, and muscle involvement allow diagnosis by inspection or scarcely invasive biopsies in about 80% of cases, whereas renal biopsy as the only diagnostic procedure is required in 20% of cases. Prevention is based on avoidance of endovascular radiology maneuvers, vascular surgery, and excess anticoagulation in atherosclerotic patients. Treatment of acute/subacute forms of renal insufficiency consisting of stopping anticoagulation and forbidding any new radiologic and/or vascular surgery procedure; treating hypertension with angiotensin 2 antagonists and vasodilators, strict volemic control by loop diuretics and ultrafiltration, along with parenteral nutrition and prednisone, has been credited with improved outcome. Iloprost may obtain favorable results. Statins definitely ameliorate the renal and patient's prognosis.
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PMID:Cholesterol crystal embolism: diagnosis and treatment. 1702 71

Renal artery stenosis (RAS) is caused by a heterogenous group of diseases with different pathophysiology, clinical manifestations, treatment approaches, and outcomes. The 2 most common forms of RAS are fibromuscular dysplasia (FMD) and atherosclerosis (ARAS). Renovascular syndromes are broadly classified into renovascular hypertension and ischemic nephropathy, but these terms are misleading, because they imply a causal relationship between RAS, hypertension, and renal dysfunction, which is difficult to prove in humans. Data supporting renal revascularization are limited by heterogeneous causes of hypertension and renal dysfunction, insufficient understanding of the relationship between RAS and nephropathy, inconsistent techniques for revascularization, ambiguous terminology and end points to assess benefit, and lack of large-scale randomized trials. The purpose of this review is to enhance understanding of the epidemiology, clinical markers, and diagnosis of RAS; the relationship between RAS and important disease states; the distinction between renal ischemia and nephropathy; optimal revascularization techniques; and avoidance of renal injury.
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PMID:Refining the approach to renal artery revascularization. 1946 23

Several autoimmune diseases are believed to be mediated, in part, by interleukin (IL)-18. Many are those with associated elevated interferon-gamma levels, such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, as well as graft-versus-host disease. Clinical and animal studies also support the concept that IL-18 is a key player in atherosclerosis, acute renal ischemia and hepatitis. IL-18 is a member of the IL-1 family; IL-1beta and IL-18 are closely related, and both require the intracellular cysteine protease caspase-1 for biologic activity. The IL-18 binding protein, a naturally occurring, specific inhibitor of IL-18, neutralizes IL-18 activities and is likely to be safe in patients. Other options for reducing IL-18 activities are inhibitors of capsase-1, human monoclonal antibodies to IL-18, soluble IL-18 receptors and anti-IL-18 receptor monoclonal antibodies.
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PMID:Interleukin-18 treatment options for inflammatory diseases. 2047 3

Atherosclerosis accounts for 90% of the cases of renal artery stenosis. It is an important cause of secondary arterial hypertension by means of inducing the renin-angiotensin system, volume expansion, and sympathetic activation. Despite high procedural success rate of renal artery stenting, clinical trials have shown an inconsistent outcome about improvement in hypertension. The accurate predictors identify the good indication for renal artery stenting is clinically needed. Currently, the presence of hemodynamically critical stenosis causing renal ischemia, the presence of symptoms with undoubtedly benefit from revascularization, and the assessment of procedural risk are key factors for decision making about indication of renal artery stenting.
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PMID:[Endovascular treatment for renal artery stenosis]. 2138 82

Adiponectin (APN) is known as an anti-inflammatory adipokine in obesity and atherosclerosis. Jin et al. examine the effects of APN deficiency in renal ischemia/reperfusion injury (IRI) using APN knockout mice and demonstrate that APN deficiency protects mice from IRI. This newly described role for APN in acute kidney injury opens up the possibility of novel mechanistic and therapeutic strategies from the cross-fertilization of the fields of obesity and kidney diseases.
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PMID:Adiponectin: an enlarging role in acute kidney injury. 2330 22

The Coral Reef Aorta is a rare phenomenon of extreme calcification in the juxtarenal and suprarenal aorta. The calcifications are often similar in appearance to growths of hyperplastic bone, though abnormalities in serum calcium are not found. [1] In contrast to the typical appearance of atherosclerosis of the great vessels, which follows the curve of the vessel wall, the calcifications of Coral Reef Aorta jut irregularly into the lumen. Consequences may include severe downstream ischemic and embolic events involving the viscera and the lower extremities, as well as endovascular operative complications. In this report we present a case of Coral Reef Aorta in a 73 year old man who experienced renal ischemia and surgical difficulties during attempted stent placement. We propose that preoperative review of vascular imaging with explicit attention to the presence of Coral Reef-like plaques can prevent intraoperative and postoperative morbidity. Furthermore, heightened awareness of the existence of these plaques on routine reads of abdominal CT or vascular imaging may prompt clinicians to enact early prophylaxis against later ischemic events.
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PMID:The Coral Reef Aorta: Diagnosis and Treatment Following CT. 2784 16

The chemokine fractalkine (CX3C chemokine ligand 1; CX3CL1) and its receptor CX3CR1 are involved in the pathogenesis of several diseases, including inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, rheumatoid arthritis, hepatitis, myositis, multiple sclerosis, renal ischemia, and atherosclerosis. There are no orally available agents that modulate the fractalkine/CX3CR1 axis. [(3S,4R)-1-[2-Chloro-6-(trifluoromethyl)benzyl]-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid (2S)-hydroxy(phenyl)acetate (E6130) is an orally available highly selective modulator of CX3CR1 that may be effective for treatment of inflammatory bowel disease. We found that E6130 inhibited the fractalkine-induced chemotaxis of human peripheral blood natural killer cells (IC50 4.9 nM), most likely via E6130-induced down-regulation of CX3CR1 on the cell surface. E6130 had agonistic activity via CX3CR1 with respect to guanosine 5'-3-O-(thio)triphosphate binding in CX3CR1-expressing Chinese hamster ovary K1 (CHO-K1) membrane and had no antagonistic activity. Orally administered E6130 ameliorated several inflammatory bowel disease-related parameters in a murine CD4+CD45RBhigh T-cell-transfer colitis model and a murine oxazolone-induced colitis model. In the CD4+CD45RBhigh T-cell transfer model, E6130 inhibited the migration of CX3CR1+ immune cells and decreased the number of these cells in the gut mucosal membrane. These results suggest that E6130 is a promising therapeutic agent for treatment of inflammatory bowel disease.
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PMID:E6130, a Novel CX3C Chemokine Receptor 1 (CX3CR1) Modulator, Attenuates Mucosal Inflammation and Reduces CX3CR1+ Leukocyte Trafficking in Mice with Colitis. 2884 93

Atherosclerotic renal artery stenosis (ARAS) can cause secondary hypertension, progressive decline in renal function, and cardiac complications. Recent randomized controlled trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study have not reported the benefit of renal artery stenting compared with medical therapy alone to improve renal function or reduce cardiovascular and renal events in the enrolled patients with ARAS. However, observational evidence indicating the benefits of angioplasty in the selected high-risk patients with ARAS has been increasing. Thus, the timely correction of stenosis through angioplasty may have a beneficial effect in selected patients. However, optimal patient selection for angioplasty has been debated and can be challenging at times. Clinicians must identify the responsive patients who would benefit from angioplasty through risk stratification and the prediction of outcomes. Efforts have been made for the determination of predictors that can identify the subgroups of patients who would benefit from angioplasty. Lower age, more severe stenosis, preserved renal perfusion, and absence of diabetes or generalized atherosclerosis have been reported as the predictors for the improvement of hypertension after angioplasty. Global renal ischemia, rapidly declining renal function over 6-12 months, progressive shrinkage of the affected kidney, lower resistive index, and lower levels of albuminuria have been reported as predictors of improved or preserved renal function after angioplasty. This review discusses the identification of ARAS patients who will potentially respond well to angioplasty.
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PMID:Selection of Patients for Angioplasty for Treatment of Atherosclerotic Renovascular Disease: Predicting Responsive Patients. 3199 95


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