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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular calcification is often encountered in the development of atherosclerotic intimal lesions. In chronic renal failure patients, vascular calcification contributes to both the morbidity and mortality. Although the molecular mechanisms regulating vascular calcification remain obscure, recent studies suggest that vascular calcification may be an actively regulated process in which vascular cells may acquire osteoblast-like functions. Several clinical studies indicate that a high serum phosphate level is highly correlated with the extent of vascular calcification and vascular disease. In vitro studies demonstrated that inorganic phosphate regulates the expression of bone matrix proteins, and that calcification is regulated by inorganic phosphate through a sodium dependent phosphate transport system. These findings suggest that inorganic phosphate may play an important role in the development of vascular calcification.
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PMID:[Vascular calcification and phosphate metabolism]. 1577 97

Until recently, vascular calcification was considered to be a passive, degenerative, and end-stage process of vascular disease. However, the observation of bone matrix proteins in calcified vascular tissues has changed this paradigm. Vascular calcification is an actively regulated process in which vascular cells may acquire osteoblast-like function. An important regulator of vascular calcification is the levels of Inorganic Phosphate (Pi). Pi directly regulates calcification through a sodium-dependent phosphate transporter system.
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PMID:[Molecular mechanism for regulation of vascular calcification]. 1577 37

Pathogenesis of the atherosclerotic process is deemed as multi-factorial, and characterized by chronic inflammatory response. Although hypertension is known to be one of the most important risk factors for atherosclerosis in causasians, its relative contribution to early atherosclerosis are still unknown. Increased evidence has indicated that hypertension, through the vasoactive peptides, such as angiotensin and endothelin-1, promotes and accelerates the atherosclerotic process via inflammatory mechanisms. In animal and human studies pro-inflammatory properties of angiotensin II has been demonstrated in large conduit and small arteries, in the kidney as well as in the heart. Activation of oxidative stress by angiotensin II is a key component of this process. Angiotensin II stimulates nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide oxidase in endothelium, smooth muscle cells, and the adventitia of blood vessel to generate reactive oxygen species, leading to endothelial dysfunction, growth, and inflammation, upregulation of endothelin-1, adhesion molecules, nuclear factor-kappa B, and other inflammatory mediators, as well as increased breakdown of nitric oxide and uncoupling of nitric oxide synthase, contribute to the progression of vascular disease and atherogenesis. In addition, recent advances concerning role of endothelin-1 as another important mediator of chronic inflammation in the vascular wall has been documented, and relationship between endothelin-1 and angiotensin II on vascular inflammation demonstrated. Inflammatory mechanisms, therefore, are important participants in the pathophysiology of hypertension-related cardiovascular disease, including atherosclerosis. In experimental models as well as human studies of atherosclerosis, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers have demonstrated the ability to prevent or reverse the progression of atherosclerosis, which was in part associated with decreased expression of inflammatory mediators and improve endothelial functions. Based on those increasing evidence, we hypothesize that inflammation may be a bridge connecting hypertension and atherosclerosis.
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PMID:Inflammation may be a bridge connecting hypertension and atherosclerosis. 1578 Apr 86

Cardiovascular disease is extremely common in patients with end-stage renal disease (ESRD) and accounts for at least 50% of deaths among these patients. Vascular calcifications (VC) have been recently implicated as a possible cause of this excess cardiovascular mortality. Medial calcification is a striking feature of vascular disease in patients with ESRD. The traditional view that VC is a degenerative and passive process has been seriously challenged, based on strong evidence suggesting that VC is an active and highly regulated process similar to bone formation. Different data support the notion that elevated levels of phosphorus and/or other uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells, which can produce bone matrix proteins. This nidus can then mineralize if the balance of pro-mineralizing factors outweighs inhibitory factors. The advent of newer noninvasive screening tests have generated great interest for screening patients with ESRD for vascular calcifications. Control of serum phosphorus with sevelamer, a recently developed non-calcium, non-aluminum phosphate binder, have attenuated or arrested progression of coronary artery and aortic calcifications compared to treatment with calcium-based binders. Amino bisphosphonates, have shown to completely inhibit soft tissue calcifications, calciphylaxis and prevent death in animal models. The first generation bisphosphonate, etidronate, reduces the progression of coronary artery calcifications patients receiving long-term hemodialysis and intravenous pamidronate has produced a rapid improvement of calciphylaxis. In conclusion, VC is a widespread phenomenon in patients with ESRD with important cardiovascular consequences. A better understanding of the processes of VC is leading to therapies to retard or improve this phenomenon and will probably have an important impact on patient mortality.
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PMID:Vascular calcifications in chronic kidney disease: are there new treatments? 1585 37

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of 2 pathways: remethylation, which requires folic acid and B-12 coenzymes, and transsulfuration, which requires pyridoxal-5'-phosphate, the B-6 coenzyme. Data from several studies suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies we have shown that plasma total homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B-6 as well as vitamin B-12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid artery stenosis of at least 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and CVD mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. This multitude of relationships between elevated plasma total homocysteine and diseases that afflict the elderly point to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is homocysteine itself or whether homocysteine is merely a marker remains to be determined.
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PMID:The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. 1670 47

Coronary artery calcification is an index of the severity of atherosclerotic vascular disease, and may predict future adverse cardiovascular events in uremic patients undergoing hemodialysis (HD). HD patients are exposed to oxidative stress, and show high plasma levels of advanced glycation end products (AGEs). The association between oxidative stress, AGEs, established cardiovascular risk factors, and coronary artery calcification score (CACS) was studied in 225 HD patients (123 male, 102 female patients). CACS was measured by using multi-detector row computed tomography. Age, systolic blood pressure, calcium, calcium x phosphate, malondialdehyde, lipid peroxides, and pentosidine were significantly and positively correlated with CACS. Duration on HD tended to be positively correlated with CACS. From the independent variables included in the forward stepwise multiple linear regression analysis, only age, systolic blood pressure, lipid peroxides, calcium, and pentosidine were independently associated with CACS. The odds ratios for past history of coronary artery disease and the presence of diabetes mellitus for high CACS (> or =100) were 6.25 (95% confidence interval; 1.83-21.4) and 2.03 (95% confidence interval; 1.02-4.05), respectively. The plasma pentosidine was significantly and positively correlated with indoxyl sulfate. In conclusion, in addition to such traditional cardiovascular risk factors as past history, diabetes mellitus, aging, systolic blood pressure and calcium overload, oxidative stress (lipid peroxides), and AGE (pentosidine) are associated with extensive coronary artery calcification in HD patients. Lipid peroxidation and glycoxidation may be involved in the pathogenesis of coronary artery calcification.
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PMID:Oxidative stress, advanced glycation end product, and coronary artery calcification in hemodialysis patients. 1672 88

An elevated calcium x phosphate product (Ca x P) is an independent risk factor for vascular calcification and cardiovascular death in dialysis patients. More physiological dialysis in patients undergoing nocturnal hemodialysis (NHD) has been shown to produce biochemical advantages compared with conventional hemodialysis (CHD) including superior phosphate (P) control. Benefits of dialysate with greater calcium (Ca) concentration are also reported in NHD to prevent Ca depletion and subsequent hyperparathyroidism, but there are concerns that a higher dialysate Ca concentration may contribute to raised serum Ca levels and greater Ca x P and vascular disease. The NHD program at our unit has been established for 4 years, and we retrospectively analyzed Ca and P metabolism in patients undergoing NHD (8-9 h/night, 6 nights/week). Our cohort consists of 11 patients, mean age 49.3 years, who had been on NHD for a minimum of 12 months, mean 34.3 months. Commencement was with low-flux (LF) NHD and 1.5 mmol/L Ca dialysate concentration, with conversion to high-flux (HF) dialyzers after a period (mean duration 18.7 months). We compared predialysis serum albumin, intact parathyroid hormone, P, total corrected Ca, and Ca x P at baseline on CHD, after conversion to LF NHD and during HF NHD. We also prospectively measured bone mineral density (BMD) on all patients entering the NHD program. Bone densitometry (DEXA) scans were performed at baseline (on CHD) and yearly after commencement of NHD. With the introduction of HF dialyzers, the Ca dialysate concentration was concurrently raised to 1.75 mmol/L after demonstration on DEXA scans of worsening osteopenia. Analysis of BMD, for all parameters, revealed a decrease over the first 12 to 24 months (N = 11). When the dialysate Ca bath was increased, the median T and Z scores subsequently increased (data at 3 years, N = 6). The mean predialysis P levels were significantly lower on LF NHD vs. CHD (1.51 vs. 1.77 mmol/L, p = 0.014), while on HF NHD P was lower again (1.33 mmol/L, p = 0.001 vs. CHD). Predialysis Ca levels decreased with conversion from CHD to LF NHD (2.58 vs. 2.47 mmol/L, p = 0.018) using a 1.5 mmol/L dialysate Ca concentration. The mean Ca x P on CHD was 4.56 compared with a significant reduction of 3.74 on LF NHD (p = 0.006) and 3.28 on HF NHD (p = 0.001 vs. CHD), despite the higher dialysate Ca in the latter. We conclude that an elevated dialysate Ca concentration is required to prevent osteopenia. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown. Better P control on NHD, however, reduces the overall Ca x P, despite the increased Ca concentration, therefore reducing the risk of vascular calcification.
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PMID:Calcium phosphate metabolism and bone mineral density with nocturnal hemodialysis. 1680 90

Chronic oxidative stress that characterizes uremia has potentially devastating effects on the vasculature and has been advocated in the pathogenesis of accelerated atherosclerosis in this disease. Recent advances have been made in our understanding of the molecular mechanisms that regulate expression and activity of key enzymes of vascular oxidative stress (eg, nicotinamide adenine dinucleotide phosphate [NAD{P}H] oxidase) and that dissect their interactions with signalling pathways of inflammation. The finding that NAD(P)H oxidase is upregulated in experimental uremia has important consequences from a physiologic and a therapeutic standpoint. In addition, identification of novel proteins involved in systemic oxidative stress has shed some new light on the pathogenesis of vascular disease. p66(shc) is a cytoplasmic protein that is expressed in a wide range of cell types. Initially believed to be involved in signalling pathways that regulate cell growth and oxidative stress, it has now been shown to play a pivotal role in promoting endothelial dysfunction and atherosclerosis. Although a specific role in uremia-related vascular disease has not yet been shown, available data in humans suggest involvement of p66(shc) in clinical conditions associated with increased oxidative stress.
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PMID:Vascular sources of oxidative stress: implications for uremia-related cardiovascular disease. 1719 33

The biological role of human paraoxonase (PON1) remains unclear, whilst there is a consensus that the enzyme has a protective influence. A toxicological role, protecting from environmental poisoning by organophosphate derivatives drove earlier works, and more recently, clinical interest has focused on a protective role in vascular disease. PON1 resides essentially on HDL particles, a complex and dynamic molecular environment. Our recent discovery of the human phosphate binding protein (HPBP), displaying a firm propensity to associate with PON1, has steered new directions for characterizing PON1 functional state. Here, we report investigations on the effect of HPBP on oligomerization, storage and thermal stability of PON1. We found that purified PON1 is as a mixture of at least two states, and that the absence of HPBP favors homo-oligomerization of PON1 into state(s) of higher molecular size. We showed that HPBP allows stabilizing active conformation(s) of PON1 disencumbered of its natural environment. We also showed that PON1 exhibits intrinsically a remarkable thermal stability, and that the association of HPBP strongly contributes to slow the denaturation rate. A hybrid recombinant PON1 was shown more thermostable than the human enzyme, and its stability was unaffected by the presence of HPBP. Altogether, the results strongly encourage further study of the human enzyme.
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PMID:Stability of highly purified human paraoxonase (PON1): association with human phosphate binding protein (HPBP) is essential for preserving its active conformation(s). 1755 53

1. Patients with chronic kidney disease (CKD) demonstrate a high burden of vascular disease. This vascular disease is unusual by way of a preponderance of medial calcification. Further, traditional cardiovascular risk factors fail to fully explain the high cardiovascular event rate in this population. 2. The present review examines the problem of medial calcification and arterial stiffness evident in patients with CKD and explores evidence for its existence and the potential pathological process involved. Many factors are emerging as potential culprits in this disease entity, although the specific roles of components such as fetuin-A, matrix Gla protein, osteopontin and fibroblast growth factor-23 have yet to be determined. Calcium and phosphate balance remains integral to the pathological process. 3. Pulse wave velocity has proven to be a useful tool to assess and follow arterial stiffness in CKD patients and is discussed. 4. Finally, techniques aimed at reducing or reversing arterial calcification and stiffness are discussed, with as yet no definitive answers available.
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PMID:Arterial calcification and stiffness in chronic kidney disease. 1758 Dec 30


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