Vascular calcification: new insights into an old problem

Proudfoot, Diane; Shanahan, Catherine M.; Weissberg, Peter L.

doi:10.1002/(sici)1096-9896(199805)185:1<1::aid-path89>3.0.co;2-j

Cited by 77 publications

(37 citation statements)

References 33 publications

(31 reference statements)

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“…34 Although calcium can be deposited into either the medial or intimal layers of the vasculature, experts hold the view that medial calcifications, rather than intimal calcifications, influence arterial stiffness. 35 Medial calcification is particularly common in diabetes mellitus and advanced renal disease, 36 and uncarboxylated (inactive) MGP is found near calcifications. 32 Circulating levels of dp-ucMGP do not affect vascular calcifications because dp-ucMGP is biologically inactive and not able to bind calcification and bone morphogenetic protein 2.…”

Section: Discussionmentioning

confidence: 99%

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population–Based Study

et al. 2015

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Increased pulse wave velocity (PWV) is the gold standard in assessing stiffening of the aorta.1 As shown by 3 population studies, all including over thousand participants, PWV refines risk stratification above and beyond traditional cardiovascular risk factors. In multivariable-adjusted analyses, per one standard deviation (SD) increment in PWV, cardiovascular mortality increased by 20% and 60% in a Danish and Taiwanese population samples, respectively.2,3 The Framingham heart study found that one standard deviation increment of PWV was associated with a 48% increase in cardiovascular disease risk. 4 Matrix Gla-protein (MGP) is acting as a strong inhibitor of soft tissue calcification. 5,6 MGP knockout mice develop massive vascular calcification in their first weeks of life and die within 2 months of vessels rupture.7 MGP is expressed primarily by chondrocytes and vascular smooth muscle cells. 8,9 To acquire its full calcification inhibitory activity, MGP needs to undergo 2 post-translational modifications: glutamate carboxylation and serine phosphorylation. Both modifications are not exerted completely, so theoretically, 4 different MGP conformations can be found: unmodified and Abstract-Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality.Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based crosssectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low-and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. inactive as desphospho-uncarboxylated MGP (dp-ucMGP), only phosphorylated, only carboxylated, and finally fully modified and active as phosphorylated and carboxylated MGP. 10,11 Carboxylation of MGP is a vitamin K-dependent process: vitamin K hydroquinone, a vitamin K m...

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Section: Discussionmentioning

confidence: 99%

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population–Based Study

et al. 2015

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“…It is however important to caution that even though certain factors may be common to the pathogenesis of valvular calcification and atherosclerotic calcification, the pathogenesis of valvular or vascular calcification in the ESRD patients treated by dialysis is likely differ- ent from the atherosclerotic calcification observed in the general population. This is evidenced by the difference in the pattern of calcification with mineral deposition mainly in the tunica media for the ESRD in contrast to calcification of the atherosclerotic plaque in the non-ESRD patients (17)(18). Hence, whether the significant association demonstrated between mitral annulus calcification and the severity of carotid (19) and aortic atheroma (10), peripheral (20) as well as coronary artery disease (21) in the general population is also applicable to patients on dialysis requires further determination.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Valve Calcification as an Important Predictor for All-Cause Mortality and Cardiovascular Mortality in Long-Term Peritoneal Dialysis Patients

Wang

Woo³

et al. 2003

Journal of the American Society of Nephrology

363

237

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Abstract. Calcification complications are frequent among longterm dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean Ϯ SD age, 55 Ϯ 12 yr) on continuous ambulatory peritoneal dialysis (mean Ϯ SD duration of dialysis, 39 Ϯ 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P Ͻ 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P Ͻ 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased allcause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P ϭ 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P ϭ 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P Ͻ 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P Ͻ 0.0005). The number of calcified valves was associated with all-cause mortality (P Ͻ 0.0005) and cardiovascular death (P Ͻ 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome. awang@cuhk.edu.hkVascular or tissue calcification is increasingly recognized to be a frequent complication in patients with end-stage renal disease (ESRD). Braun et al. (1) reported that two thirds of the adult hemodialysis patients had electron beam computed tomographic (EBCT) evidence of coronary artery calcification (CAC) and that over half had cardiac valve calcification. The calcification score in dialysis patients was not only substantially higher than age-matched and gender-matched patients with angiographically confirmed c...

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“…Recent investigations have revealed that the mechanism of vascular calcification is similar to that of osteogenesis (7). Due to the presence of collagenous and noncollagenous proteins associated with bone mineralization in vascular smooth muscle cells (SMCs), vascular SMCs within developing atherosclerotic plaques play an important role in the deposition of extracellular matrix, resulting in vascular calcification (8).…”

Section: Introductionmentioning

confidence: 99%

Calcification of Aortic Smooth Muscle Cells Isolated From Spontaneously Hypertensive Rats

et al. 2008

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Abstract. Although hypertension and vascular calcification are well established as important risk factors for several cardiovascular diseases, the relationship between them is unknown. Here, we investigated whether hypertension is relevant to vascular calcification by examining aortic smooth muscle cells (SMCs) isolated from the descending thoracic aortas of Wistar Kyoto rats (WKY) as normotensive rats and spontaneously hypertensive rats (SHR), a typical rat model of hypertension. Cells were cultured in DMEM containing 10% FBS for 6 days after reaching confluence. Von Kossa staining revealed that the positively stained calcified area of aortic SMCs from SHR increased rapidly compared to that from WKY. The gene expressions of calcificationregulating proteins including msh homeobox homolog 2, Osterix (a master transcription factor for osteogenesis), and alkaline phosphatase (ALP) (a marker of vascular calcification) were significantly increased in aortic SMCs from SHR compared to SMCs from WKY. On the other hand, Runx2, another osteogenic transcription factor, did not upregulate. Furthermore, we confirmed that ALP activity was strongly increased in aortic SMCs from SHR compared to SMCs from WKY. These results suggest that aortic SMCs from SHR tend to become easily calcified via an Msx2-Osterix signaling pathway.

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Vascular calcification: new insights into an old problem

Cited by 77 publications

References 33 publications

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population–Based Study

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population–Based Study

Cardiac Valve Calcification as an Important Predictor for All-Cause Mortality and Cardiovascular Mortality in Long-Term Peritoneal Dialysis Patients

Calcification of Aortic Smooth Muscle Cells Isolated From Spontaneously Hypertensive Rats

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