Cartilaginous metaplasia in calcified diabetic peripheral vascular disease: Morphologic evidence of enchondral ossification

Qiao, Jian-Hua; Mertens, Richard B.; Fishbein, Michael C.; Geller, Stephen A.

doi:10.1053/hupa.2003.72

Cited by 74 publications

(65 citation statements)

References 23 publications

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“…136,137 The simultaneous upregulation of chondrocyte-specific markers and suppression of the osteoblast differentiation pathway led us to the hypothesis that medial smooth muscle cells more likely transdifferentiate into chondrocyte-like cells than having an osteoblast-like fate during uremia-related medial calcification. 92 Evidence for the expression of a chondrogenic phenotype in intimal and medial calcified lesions is also shown in arteries from diabetics 138,139 and transplant donors. 102 However, cartilage metaplasia might be just one of the pathological pathways causing vascular calcification.…”

Section: Search For Mechanisms Of Vascular Calcificationmentioning

confidence: 97%

Vascular Calcification in Chronic Renal Failure

Neven

D’Haese

2011

Circulation Research

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Accelerated atherosclerotic plaque calcification and extensive medial calcifications are common and highly detrimental complications of chronic kidney disease. Valid murine models have been developed to investigate both pathologically distinguishable complications, which allow for better insight into the cellular mechanisms underlying these vascular pathologies and evaluation of compounds that might prevent or retard the onset or progression of vascular calcification. This review describes various experimental models that have been used for the study of arterial intimal and/or medial calcification and discusses the extent to which this experimental research has contributed to our current understanding of vascular calcification, particularly in the setting of chronic renal failure. (Circ Res. 2011;108:249-264.) Key Words: animal models Ⅲ vascular calcification Ⅲ chronic renal failure C ardiovascular disease is the main cause of morbidity and mortality in patients with chronic kidney disease (CKD), accounting for approximately 50% of all deaths in patients on dialysis and in recipients of renal transplants. 1 A large-scale prospective population-based study showed that renal function was inversely associated with cardiovascular and allcause mortality. 2 Vascular calcification is the major cause of cardiovascular disease in patients with CKD as it contributes to myocardial ischemia, impaired myocardial function, valvular insufficiency, arrhythmias and stroke and is shown to be a strong independent predictor of mortality in the general 3,4 as well as in the dialysis population. [5][6][7] In patients with endstage renal disease, the risk of death increases with the number of vascular sites affected by calcification in the aorta and the carotid and femoral arteries. 5 The high prevalence of vascular calcification is already reported in early stages of CKD 8,9 and in young dialysis patients. 10,11 Atherosclerotic plaque burden in the intimal layer is higher and these lesions are also more heavily calcified in CKD patients compared to the normal population. 12-14 Although intimal calcification is associated with cardiovascular mortality, 6 it remains controversial whether calcification of advanced atherosclerotic lesions stabilizes plaque vulnerability [15][16][17] or rather contributes to rupture of the fibrous cap, 18,19 leading to thrombotic events and myocardial infarction. Interestingly, Ehara et al 20 nicely showed that the pattern of calcification in the intimal plaque is of importance: small, frequent, spotty calcifications are more often found in patients with an acute myocardial infarction or with unstable angina pectoris, whereas the presence of extensive calcifications was highest in those with stable angina pectoris. Recent investigations add new insights to this observation and indicate that, in contrast to spacious calcified areas, sparse microcalcifications produce local stress, 21 activate macrophages to secrete inflammatory mediators 22 and induce apoptosis of vascular smooth muscle cells, 23...

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Section: Search For Mechanisms Of Vascular Calcificationmentioning

confidence: 97%

Vascular Calcification in Chronic Renal Failure

Neven

D’Haese

2011

Circulation Research

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“…35 Transitional stages between amorphous calcification and mature bone tissue are also seen, the latter apparently requiring microvascular invasion as in skeletal bone. Although less common than bone, ectopic cartilage also occurs in human vascular calcification, 36 and it is the predominant form of ectopic mineralized tissue in mice, 37 especially in the brachiocephalic arteries of apolipoprotein E (apoE)-null mice. 38 Thus, by structural, molecular, and cellular criteria, vascular calcification proceeds via active osteochondrogenic processes.…”

Section: Vascular Calcification Compared With Skeletal Calcificationmentioning

confidence: 99%

Vascular Calcification

2008

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M ost individuals aged Ͼ60 years have progressively enlarging deposits of calcium mineral in their major arteries. 1 This vascular calcification reduces aortic and arterial elastance, which impairs cardiovascular hemodynamics, resulting in substantial morbidity and mortality [2][3][4] in the form of hypertension, aortic stenosis, cardiac hypertrophy, myocardial and lower-limb ischemia, congestive heart failure, and compromised structural integrity. [5][6][7] The severity and extent of mineralization reflect atherosclerotic plaque burden 8 and strongly and independently predict cardiovascular morbidity and mortality. 9 Previously considered passive and degenerative, vascular calcification is now recognized as a pathobiological process sharing many features with embryonic bone formation. As evidence of this change in paradigm, research on vascular calcification has accelerated dramatically in the past decade. A search of PubMed (www.ncbi.nlm.nih.gov; US National Library of Medicine) under the key words vascular calcification returned Ϸ16 articles in 1982, 100 in 1994, and 250 in 2004. This year, 400 new publications are expected, for a total Ͼ3500.A breakthrough in this field was the recognition of its similarity to bone development and metabolism, in which endothelial, mesenchymal, and hematopoietic cells interact and respond to mechanical, inflammatory, metabolic, and morphogenetic signals governing skeletal mineralization; their counterparts in the artery wall govern arterial mineralization. With increasing age and dysmetabolic conditions in our population, the clinical burden of vascular calcification will continue to increase. Clinical Impact of Arterial CalcificationAortic calcification promotes congestive heart failure by eroding compliance and elastance. The hemodynamic demands of the cardiovascular system require that the aorta store energy in its elastance during systole and release it during diastole, which minimizes cardiac work and is the basis for balloon counterpulsation. This function, known as Windkessel physiology, is reflected in the high density of elastin in the arch, where mechanical energy is highest. Its loss is detectable as increased arterial pulse wave velocity in calcified arteries, resulting in thoracic summation of reflected and orthograde pressure waves, thereby increasing systolic and pulse pressures. It also increases cardiac work, promoting heart failure, left ventricular hypertrophy, and diastolic dysfunction, independently of atherosclerosis, aging, or diabetes. The link between aortic rigidity and heart failure is most evident in the hypertensive cardiomyopathy observed in patients with idiopathic infantile arterial calcification and in animal models with aortic banding.In the aortic valve, calcification produces life-threatening aortic stenosis. Although previously considered a passive, degenerative, untreatable disorder of "wear and tear" unrelated to atherosclerosis, recent findings now show that valvular calcification is regulated in a manner similar to that of atheroscler...

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“…Recent evidence suggests that both of these cell types may play a similar role in mediating the calcification of atherosclerotic lesions in humans and mice. 10 Chondrocyte metaplasia within blood vessels has been previously reported in humans 11 and is frequently observed in mouse models of atherosclerosis. [12][13][14] The designation of these cells as chondrocytes is based on the morphological similarity to chondrocytes in cartilage and on the presence of cartilage and bone extracellular matrix proteins.…”

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confidence: 99%