Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction (ED) is a common condition with a significant effect on quality of life. The prevalence of ED increases with age and other risk factors (hypertension, diabetes, smoking, coronary heart disease, dyslipidemia and depression). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. Endothelial dysfunction and a reduced generation or bioavailability of NO have emerged as major pathophysiological mechanisms in ED. Hyperlipidemia may impair erectile function by affecting endothelial and smooth muscle cells of the penis. Oxidized low-density lipoprotein is a causative factor for the impaired relaxation response of the corpus cavernosum. Elevated serum cholesterol and reduced high density lipoprotein cholesterol levels are associated with an increased risk of ED. It follows that treating dyslipidemia could have a beneficial effect on ED. Phosphodiesterase type 5 inhibitors are now considered as first line treatment for ED. There is evidence that statins improve responses to these drugs. ED is considered as a warning sign of silent or early vascular disease. The use of statins may be beneficial in these patients.
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PMID:Dyslipidemia as a risk factor for erectile dysfunction. 1762 14

The migraine-ischemia relationship is best understood in the context of the pathophysiology of migraine. Potential mechanisms of migrainous infarction (stroke occurring during migraine) include vasospasm, hypercoagulability, and vascular changes related to cortical spreading depression. Stroke occurring remote for the migraine attack may be related to arterial dissection, cardioembolism, and endothelial dysfunction. Endothelial dysfunction, a process mediated by oxidative stress, may be a cause or a consequence of migraine, and explain the relationship of migraine to vascular factors and ischemic heart disease. It remains uncertain whether stroke or myocardial infarction can be prevented by migraine prophylaxis, endothelial repair, platelet inhibition, or a combination of these strategies. Although triptans are generally considered safe for use in migraine, caution is warranted in those with multiple vascular risk factors. Known vascular disease is a contraindication to triptan use.
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PMID:Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. 1766 75

Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis. Among imaging techniques, the early determination of common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and nitroglycerine-mediated vasodilation (NMD) may be useful to determine atherosclerosis and endothelial dysfunction. We and others found increased ccIMT and impaired FMD in RA patients. Among immunological and metabolic laboratory markers, anticyclic citrullinated peptide (anti-CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), Th0/Th1 T cells, homocysteine, dyslipidemia, decreased folate and vitamin B12 production, and impaired paraoxonase activity may all be involved in the development of vascular disease in RA. The early diagnosis of endothelial dysfunction and atherosclerosis, active immunosuppressive treatment, the use of drugs that control atherosclerosis, changes in sedentary lifestyle, and the close follow-up of RA patients may help to minimize cardiovascular risk in these individuals.
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PMID:Accelerated atherosclerosis in rheumatoid arthritis. 1789 98

Endothelial dysfunction is a major feature of vascular diseases. A practical, minimally invasive method to effectively "probe" gene transcription for an individual patient's endothelium has potential to "customize" assessment for an individual at risk of vascular disease as well as pathophysiologic insight in an in vivo human, clinical context. Published literature lacks a methodology to identify endothelial differential gene expression in individuals with vascular disease. We describe a methodology to do so. The aim of this study was to specifically utilize (a) cutaneous microvascular biopsy, (b) laser capture microdissection, (c) cDNA amplification, (d) suppression subtractive hybridization, (e) high-throughput sequencing techniques, (f) real-time polymerase chain reaction (PCR), and (g) in combination of these methods, to profile differential gene expression in the context of cardiovascular and cerebrovascular disease. Endothelial cells were obtained by laser capture microdissection from a patient and a healthy sibling's microvascular biopsy tissues. Endothelial RNA was extracted, reverse transcribed, and amplified to ds cDNA. Suppression subtractive hybridization was used to establish an endothelial differential gene expression library. Real-time PCR confirmed SERP1, caspase 8, IGFBP7, S100A4, F85, and F147 up-regulation between 1.4- and 3.47-fold. The authors have successfully established a methodology to profile endothelial differential gene expression and identified six differentially expressed genes. This minimally invasive novel method has potential wide application in the customized assessment of many patients suffering vascular diseases.
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PMID:A novel methodology to probe endothelial differential gene expression profile reveals novel genes. 1808 Aug 67

There is increased awareness regarding the close association between cardiovascular disease and erectile dysfunction, especially because both conditions share common risk factors such as diabetes mellitus, hypertension, smoking, hyperlipidemia, and a sedentary lifestyle. Recent studies suggest that erectile dysfunction could be considered a potential marker for underlying silent cardiac or vascular disease processes. Endothelial dysfunction seems to play a major role in both sexual dysfunction and heart disease. With the initiation in 1998 of vasoactive drugs such as the phosphodiesterase-5 inhibitors for the treatment of erectile dysfunction, the underlying vascular components of erectile dysfunction have become a more prominent focus of attention in the clinical and research setting. This review critically examines the background, pathophysiology, and mechanisms behind erectile dysfunction and its close correlation to cardiovascular disease.
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PMID:The relationship between erectile dysfunction and cardiovascular disease. Part I: pathophysiology and mechanisms. 1819 44

Platelet activation induces rapid thrombus formation at a ruptured atherosclerotic plaque leading to acute vessel occlusion and a fatal or non-fatal cardiovascular event. More recent evidence suggests that activated platelets play an additional central role during the initiation of atherosclerosis, essentially facilitating leukocyte adhesion and recruitment. Endothelial dysfunction is a common and early feature of cardiovascular diseases characterized by reduced bioavailability of prostacyclin and nitric oxide (NO). Subsequently impaired endogenous platelet inhibition causes platelet activation in pre-atherosclerotic vascular disease resulting in enhanced platelet susceptibility to agonists released from the inflamed endothelium. Platelet adhesion to inflammatory, dysfunctional endothelium precedes leukocyte adhesion. Indeed, adherent activated platelets are mandatory for leukocyte recruitment in the early phases of atherosclerosis under arterial flow conditions. Increased expression of chemokines in atherosclerotic plaques and the inflamed endothelium initiates and facilitates pro-inflammatory processes in leukocytes and the vascular wall. Apart from their chemotactic properties, some chemokines such as fractalkine contribute to platelet activation. Moreover, fractalkine induces leukocyte recruitment to inflamed endothelial cells under arterial flow by activating adherent platelets. An aggressive form of atherosclerosis is found in patients with diabetes. Since diabetes is currently considered as a risk equivalent for coronary artery disease, the interaction between oxidative stress, endothelial dysfunction, impaired endogenous platelet inhibition and platelet activation is discussed in the light of diabetes. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis, the major complication of atherosclerosis triggering myocardial infarction and stroke.
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PMID:Endothelial dysfunction, impaired endogenous platelet inhibition and platelet activation in diabetes and atherosclerosis. 1822 Sep 40

Endothelial dysfunction plays a central role in diabetic vascular disease, but its molecular bases are not completely defined. We showed previously that the actin-binding protein proflin-1 was increased in the diabetic endothelium and that attenuated expression of profilin-1 protected against atherosclerosis. Also 7-ketocholesterol up-regulated profilin-1 in endothelial cells via transcriptional mechanisms. The present study addressed the pathways responsible for profilin-1 gene expression in 7-ketocholesterol-stimulated endothelial cells and in the diabetic aorta. In luciferase reporter assays, the response to 7-ketocholesterol within the 5'-flanking region of profilin-1 was dependent on a single STAT response element. In aortic endothelial cells, 7-ketocholesterol enhanced STAT3 activation, which required JAK2 and tyrosine 394 phosphorylation of oxysterol-binding protein-1. These changes were recapitulated in the aorta of diabetic rats. Also 7-ketocholesterol in cultured endothelial cells and diabetes in the aorta elicited the recruitment of STAT3 and relevant coregulatory factors to the oxysterol-responsive region of the profilin-1 promoter. These events were required for profilin-1 up-regulation. These studies identify a previously unrecognized oxysterol-binding protein-mediated mode of activation of STAT3 that controls the expression of the proatherogenic protein profilin-1 in response to 7-ketocholesterol and the diabetic milieu.
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PMID:Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. 1823 Jun 13

S100A1, a Ca(2+)-binding protein of the EF-hand type, is known to modulate sarcoplasmic reticulum Ca(2+) handling in skeletal muscle and cardiomyocytes. Recently, S100A1 has been shown to be expressed in endothelial cells (ECs). Because intracellular Ca(2+) ([Ca(2+)](i)) transients can be involved in important EC functions and endothelial NO synthase activity, we sought to investigate the impact of endothelial S100A1 on the regulation of endothelial and vascular function. Thoracic aortas from S100A1 knockout mice (SKO) showed significantly reduced relaxation in response to acetylcholine compared with wild-type vessels, whereas direct vessel relaxation using sodium nitroprusside was unaltered. Endothelial dysfunction attributable to the lack of S100A1 expression could also be demonstrated in vivo and translated into hypertension of SKO. Mechanistically, both basal and acetylcholine-induced endothelial NO release of SKO aortas was significantly reduced compared with wild type. Impaired endothelial NO production in SKO could be attributed, at least in part, to diminished agonist-induced [Ca(2+)](i) transients in ECs. Consistently, silencing endothelial S100A1 expression in wild type also reduced [Ca(2+)](i) and NO generation. Moreover, S100A1 overexpression in ECs further increased NO generation that was blocked by the inositol-1,4,5-triphosphate receptor blocker 2-aminoethoxydiphenylborate. Finally, cardiac endothelial S100A1 expression was shown to be downregulated in heart failure in vivo. Collectively, endothelial S100A1 critically modulates vascular function because lack of S100A1 expression leads to decreased [Ca(2+)](i) and endothelial NO release, which contributes, at least partially, to impaired endothelium-dependent vascular relaxation and hypertension in SKO mice. Targeting endothelial S100A1 expression may, therefore, be a novel therapeutic means to improve endothelial function in vascular disease or heart failure.
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PMID:Endothelial S100A1 modulates vascular function via nitric oxide. 1829 99

Erectile dysfunction is a common problem affecting sexual function in men. Approximately one in 10 men over the age of 40 is affected by this condition and the incidence is age related. Erectile dysfunction is a sentinel marker for several reversible conditions including peripheral and coronary vascular disease, hypertension and diabetes mellitus. Endothelial dysfunction is a common factor between the disease states. Concurrent conditions such as depression, late-onset hypogonadism, Peyronie's disease and lower urinary tract symptoms may significantly worsen erectile function, other sexual and relationship issues and penis dysmorphophobia. A focused physical examination and baseline laboratory investigations are mandatory. Management consists of initiating modifiable lifestyle changes, psychological and psychosexual/couples interventions and pharmacological and other interventions. In combination and with treatment of concurrent comorbid states, these interventions will often bring about successful resolution of symptoms and avoid the need for surgical interventions.
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PMID:Erectile dysfunction. 1839 56

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy. Endothelial-derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with endothelial dysfunction. We evaluated the association of the constitutive endothelial nitric oxide synthase gene (eNOS) polymorphisms with type 2 diabetic nephropathy. We genotyped three polymorphisms of eNOS (Two SNPs: -786T > C, 894G > T and one 27-bp repeat polymorphism in Intron 4 (27VNTR)) in type 2 diabetic nephropathy patients (cases: n = 195) and type 2 diabetic without nephropathy (controls: n = 255), using validated PCR-RFLP assays. We measured serum NO levels in these subjects and examined its correlation with diabetic nephropathy and eNOS genotypes. The frequency of CC (-786T > C), TT (894G > T) and aa genotypes (27VNTR) were significantly higher in diabetic nephropathy patients as compared to the diabetes without nephropathy group (CC: P = 0.003, TT: P = 0.03, aa: P < 0.0001). These mutant genotypes were found to be associated with higher risk of nephropathy (-786T > C: OR: 5.5, 95%CI: 1.53-19.79; 894G > T: OR: 1.8, 95%CI: 1.03-3.16; Intron 4: OR: 6.23, 95%CI: 2.23-16.31). Haplotype with all the wild alleles (T-b-G) was found to be associated with a decreased risk of nephropathy (OR: 0.68, P = 0.005) and haplotype with all mutant alleles (C-a-T) was associated with higher risk of diabetic nephropathy as compared to diabetes without nephropathy group (OR: 2.6, P = 0.14). No significant linkage disequilibria were observed among the variants in this case-control study. The serum NO levels were observed to be significantly (P < 0.05) lower in mutant allele carriers ('C' allele of T-786C SNP and/or 'T' allele of G894T SNP) as compared with the wild-type allele carriers (-786T and/or 894G) within each of the subject groups (with and without nephropathy). These results suggest that the eNOS gene locus is associated with diabetic nephropathy and the functional polymorphisms (-786T > C & 894G > T) might lead to a decreased expression of eNOS gene.
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PMID:Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians. 1840 56


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