Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular calcification increasingly afflicts our aging and dysmetabolic population, predisposing patients to cardiovascular mortality and lower extremity amputation. Active osteogenic processes are evident in most histoanatomic variants, including elaboration of BMP2-Msx2 signals required for craniofacial bone formation. We developed an animal model of diet-induced diabetes, dyslipidemia, and vascular calcification. High-fat diets promote vascular calcification in male low-density lipoprotein receptor (LDLR)-deficient mice, with concomitant upregulation of aortic BMP2 and Msx2 gene expression. We wished to test if Msx2 exerts pro-calcific actions during vascular calcification, as it does in craniofacial bone. We studied CMV-Msx2Tg+;LDLR+ transgenic mice (C57Bl/6), a model previously demonstrated to recapitulate features of Msx2 signaling during craniosynostosis. After 16 weeks of fatty diets, vascular calcification was studied in CMV-Msx2Tg+ versus nontransgenic sibs. Only CMV-Msx2Tg+ mice fed high-fat diets exhibited vascular calcium accumulation by alizarin red staining, noted in the tunica media of coronary arteries and the aorta. Gene expression studies revealed that while Msx2 was expressed primarily in adventitial cells, alkaline phosphatase (ALP) expression and calcification occurred primarily in the tunica media. Msx2 promotes the elaboration of a pro-osteogenic milieu by upregulating expression of Wingless type (Wnt) ligands while downregulating the canonical antagonist, Dickkopf (Dkk1). Msx2 upregulates aortic Wnt signaling in vivo, revealed by the analysis of TOPGAL+ (Wnt reporter) versus CMV-Msx2Tg+; TOPGAL+ mice. Aortic Msx2 exerts pro-osteogenic signaling in vivo and in vitro, mediated in part via the enhancement of paracrine Wnt signaling. Strategies that selectively inhibit aortic Msx2-Wnt cascades may help diminish the initiation and progression of diabetic vascular disease.
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PMID:Osteogenic regulation of vascular calcification. 1683 33

Vascular calcification (VC) is an orchestrated event, evoking the programmed process of the osteogenesis and triggered by inflammatory cytokines active at vascular level. VC is a dynamic process in which the vessel wall intima, media and also cardiac valves may be involved. Intimal calcification is an endochondral ossification process in which type II collagen is mineralized by calcium deposition. In contrast, an intra-membranous ossification process leads to medial calcification, while a dystrophic calcification process is responsible for valvular calcification. Mechanisms involved in VC may be summarized as: 1. Activation of osteogenesis in the vessel wall, 2. Loss of inhibitory factors, 3. Enhanced bone turnover, and 4. Abnormalities in mineral metabolism. The signaling axis constituted by osteoprotegerin (OPG), receptor activator nuclear factor kB (RANK) and its ligand (RANKL), along with the monocyte colony stimulating factor (M-CSF) and the transcription factor core Binding protein (Cbfa-1), play a pivotal role in the control of VC. In contrast, fetuin-A, matrix G1a protein (MGP) and osteopontin (OPN) control the inhibition of VC. In addition, abnormal mineral metabolism with enhanced phosphates availability favors calcium deposition. The inflammatory cytokines interleukin (IL-1) and tumor necrosis factor (TNF)-alpha enhance OPG and RANKL function in the vessel wall leading to VC. VC is a controlled process, depending on the balance between osteoblastic and osteoclastic influences and further modulated by the influence of risk factors like diabetes, smoking, age, hypertension and dyslipidemia. Recent advances in diagnostic tools such as with multi-detector computed tomography (MDCT) and electron beam computed tomography (EBCT), may help diagnosis and delineation of VC in the clinical setting and aid in understanding its prognostic value.
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PMID:Molecular determinants of vascular calcification: a bench to bedside view. 1691 72

Free fatty acids (FFAs) play important physiological roles in many tissues as an energy source and as signaling molecules in various cellular processes. Elevated levels of circulating FFAs are associated with obesity, dyslipidemia, and diabetes. Here we show that GPR84, a previously orphan G protein-coupled receptor, functions as a receptor for medium-chain FFAs with carbon chain lengths of 9-14. Medium-chain FFAs elicit calcium mobilization, inhibit 3',5'-cyclic AMP production, and stimulate [35S]guanosine 5'-O-(3-thiotriphosphate) binding in a GPR84-dependent manner. The activation of GPR84 by medium-chain FFAs couples primarily to a pertussis toxin-sensitive G(i/o) pathway. In addition, we show that GPR84 is selectively expressed in leukocytes and markedly induced in monocytes/macrophages upon activation by lipopolysaccharide. Furthermore, we demonstrate that medium-chain FFAs amplify lipopolysaccharide-stimulated production of the proinflammatory cytokine interleukin-12 p40 through GPR84. Our results indicate a role for GPR84 in directly linking fatty acid metabolism to immunological regulation.
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PMID:Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. 1696 19

Several groups have demonstrated an association between established CHD and elevated oxidized LDL (oxLDL). The relation with cardiovascular risk factors and subclinical CVD is less clear. Therefore, we examined this association in the Multi-Ethnic Study of Atherosclerosis cohort: 879 persons without CHD, all non-statin users, examined cross-sectionally. oxLDL was measured with a monoclonal antibody 4E6-based ELISA. The presence of subclinical CVD was defined as plaque occurrence in carotid arteries with > or = 25 stenosis, ankle-brachial blood pressure index (ABI) < 0.9 and coronary calcification based on Agatston calcium score > or = 200. In a multivariate model, dyslipidemia (adverse levels of cholesterol, HDL-cholesterol, triglycerides), inflammation (elevated fibrinogen), gender (male), ethnicity (Black), and current smoking explained the most variation in oxLDL (model R2=0.41). In bivariate analyses, persons with subclinical CVD had higher levels of oxLDL (1.22 mg/dl versus 0.95 mg/dl; P=0.0002). Adjustment for risk factor correlates attenuated associations with subclinical CVD (P=0.026). In conclusion, oxLDL is associated with subclinical CVD by its relationship with many cardiovascular risk factors.
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PMID:The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups: the Multi-Ethnic Study of Atherosclerosis (MESA). 1698 59

The presentation of primary hyperthyroidism (PHPT) has changed substantially in the last decade. Before the introduction of routine calcium measurement in most automated biochemistry serum analyzers, it usually was diagnosed after renal and bony lesions already were present. Nowadays, its presentation is practically asymptomatic. Nevertheless, the cardiovascular morbidity and mortality of mild to moderate forms of PHPT reportedly are increasing. Individuals who have mild to moderate forms of PHPT have an increased risk for enduring cardiovascular disease, arterial hypertension, left ventricular hypertrophy, myocardial and valvular calcifications, altered vascular reactivity, and cardiac conduction. Finally, they also reveal alterations in carbohydrate metabolism, insulin resistance, dyslipidemia, and body composition.
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PMID:Primary hyperparathyroidism, insulin resistance, and cardiovascular disease: a review. 1727 May 92

Many epidemiological studies have shown an association between osteoporosis and vascular calcification or atherosclerotic diseases (coronary heart disease, stroke, peripheral vascular disease) in the elderly or postmenopausal women. These results indicate that osteoporosis and atherosclerosis might be linked by common risk factors or pathological mechanisms. Dyslipidemia has the correlation to both osteoporosis and atherosclerosis. Statins, nitorogen-containing bisphosphonates, and estrogens have the favorable effects on lipid profiles as well as vasculature, or bone mineral density. Thus, these therapeutic approaches might have dual effects on bone and vasculature.
Clin Calcium 2007 Mar
PMID:[Osteoporosis and atherosclerosis]. 1733 38

This is the report of an 11-year-old boy with chronic renal disease and secondary hyperparathyroidism. The child had been on dialysis, calcitriol, calcium carbonate, and presented dyslipidemia and calcified thrombi in various vessels and organs in the course of his condition. Pathological examination showed ischemic cerebral necrosis, calcification in coronary arteries, and myocardial infarction.
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PMID:Cardiovascular complications in a child with chronic renal failure. 1738 23

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. This syndrome is occurring at epidemic rates, with dramatic consequences for human health worldwide, and appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in fructose intake, which appears to be an important causative factor in the metabolic syndrome. There is also experimental and clinical evidence that the amount of magnesium in the western diet is insufficient to meet individual needs and that magnesium deficiency may contribute to insulin resistance. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenic factor in the development of metabolic syndrome. Pro-inflammatory molecules produced by adipose tissue have been implicated in the development of insulin resistance. The present review will discuss experimental evidence showing that the metabolic syndrome, high fructose intake and low magnesium diet may all be linked to the inflammatory response. In many ways, fructose-fed rats display the changes observed in the metabolic syndrome and recent studies indicate that high-fructose feeding is associated with NADPH oxidase and renin-angiotensin activation. The production of reactive oxygen species results in the initiation and development of insulin resistance, hyperlipemia and high blood pressure in this model. In this rat model, a few days of experimental magnesium deficiency produces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines, appearance of the acute phase proteins and excessive production of free radicals. Because magnesium acts as a natural calcium antagonist, the molecular basis for the inflammatory response is probably the result of a modulation of the intracellular calcium concentration. Potential mechanisms include the priming of phagocytic cells, the opening of calcium channels, activation of N-methyl-D-aspartate (NMDA) receptors, the activation of nuclear factor-kappaB (NFkB) and activation of the renin-angiotensin system. Since magnesium deficiency has a pro-inflammatory effect, the expected consequence would be an increased risk of developing insulin resistance when magnesium deficiency is combined with a high-fructose diet. Accordingly, magnesium deficiency combined with a high-fructose diet induces insulin resistance, hypertension, dyslipidemia, endothelial activation and prothrombic changes in combination with the upregulation of markers of inflammation and oxidative stress.
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PMID:High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. 1740 91

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.
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PMID:The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. 1740 90

Increased aortic stiffness, as measured by pulse wave velocity (PWV) and augmentation index (Aix), and vascular calcification have been associated with an unfavourable cardiovascular outcome in hemodialysis patients. However, the majority of data have been published in white patients and epidemiological data are discordant on the fate of patients of different races. In this cross sectional study we measured PWV and Aix by applanation tonometry and coronary artery and thoracic aorta calcium score (CAC and AoC) by electron beam tomography (EBT) in 81 Blacks and 61 Whites on maintenance hemodialysis. Vascular stiffness measurements and EBT scans were performed within a week of each other. There was no difference between races in age, systolic blood pressure or gender distribution. Blacks had a more frequent history of hypertension (100% versus 89%; P=0.002), lower prevalence of dyslipidemia (30% versus 66%; P<0.001), higher PTH levels (geometric mean 607 pg/ml versus 245 pg/ml; P=0.039), received calcium based phosphate binders less frequently (37% versus 60%, P=0.007) and calcium antagonists more frequently than Whites (54% versus 28%; P=0.003). Nonetheless, the unadjusted and risk adjusted PWV and Aix, as well as CAC and AoC were not statistically different between races. In this dialysis cohort there was no difference in markers of vasculopathy between black and white patients despite differences in baseline clinical characteristics. Epidemiological data from the general population indicate that Blacks have lower calcium scores and stiffer vessels than Whites. Some studies in the renal populations suggest a better and others a similar survival of Blacks and Whites on hemodialysis. Our findings raise the important question of the prognostic significance of markers of vasculopathy in patients of different races and with different risk profiles.
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PMID:Markers of vascular disease do not differ in black and white hemodialysis patients despite a different risk profile. 1752 8


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