Calciotropic Hormones and Arterial Physiology

Towler, Dwight A.

doi:10.1681/asn.2006121367

Cited by 12 publications

(11 citation statements)

References 41 publications

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“…Panel A, both calcitriol excess and deficiency have been associated with cardiovascular disease 141, 212 , recently confirmed in children with CKD 213 . Panel B, similar cardiovascular problems arise with either both excesses 196 and insufficiencies 127, 128 in PTH.…”

Section: Figurementioning

confidence: 86%

Arterial calcification and bone physiology: role of the bone–vascular axis

2012

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Bone never forms without vascular interactions. This simple statement of fact does not adequately reflect the physiological and pharmacological implications of the relationship. The vasculature is the conduit for nutrient exchange between bone and the rest of the body. The vasculature provides the sustentacular niche for development of osteoblast progenitors, and is the conduit for egress of bone marrow cell products arising, in turn, from the osteoblast-dependent hematopoietic niche. Importantly, the second most calcified structure in humans after the skeleton is the vasculature. Once considered a passive process of dead and dying cells, vascular calcification has emerged as an actively regulated form of tissue biomineralization. Skeletal morphogens and osteochondrogenic transcription factors are elaborated by cells within the vessel wall, regulating the deposition of vascular calcium. Osteotropic hormones including parathyroid hormone regulate both vascular and skeletal mineralization. Cellular, endocrine, and metabolic signals flow bidirectionally between the vasculature and bone that are necessary for both bone health and vascular health. Dysmetabolic states including diabetes, uremia, and hyperlipidemia perturb the bone-vascular axis, giving rise to devastating vascular and skeletal disease. A detailed understanding of bone-vascular interactions is needed to address the unmet clinical needs of our increasingly aged and dysmetabolic population.

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Section: Figurementioning

confidence: 86%

Arterial calcification and bone physiology: role of the bone–vascular axis

2012

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“…Toxic levels of vitamin D induce arterial calcification, and this may involve the stimulation of matrix vesicles, which then act as mineral nucleation sites (118). This effect of hypervitaminosis D is exploited in the VDN model.…”

Section: Hypervitaminosis D Plus Nicotine (Vdn Model)mentioning

confidence: 99%

Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences

Atkinson¹

2008

Journal of Applied Physiology

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Atkinson J. Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences. J Appl Physiol 105: 1643-1651, 2008. First published September 4, 2008 doi:10.1152/japplphysiol.90476.2008.-With age, the calcium content of the arterial wall increases. Calcification occurs at two main levels: intimal plaques and the medial elastic fiber network. The latter has been referred to as medial elastocalcinosis and is the subject of this review. The mechanisms involved in elastocalcinosis are complex and involve polar, apolar, and active processes. Vascular calcification may be species specific to humans. As laboratory animals, such as the rat, grow old, they suffer from only very mild arterial calcification. Different animal models of induction of massive arterial calcification by pharmacological and other means exist. Although extrapolation from such models to the clinical situation in terms of etiology is difficult, such models could be useful in the nonclinical study of the pathophysiological consequences of vascular calcification. Vascular calcification modifies arterial wall stiffness, and this could have clinically significant consequences on cardiac function and downstream circulatory control.artery; calcium; wall stiffness; aging Development of the Concept of ElastocalcinosisSeveral recent reviews deal with the subject of elastocalcinosis (1,21,25,41,54,56,82,108).Age-linked vascular calcification has been known since the nineteenth century (85,122). It appears to be "specific" in that vascular wall calcium and phosphorus contents increase with age, whereas there are no significant increases in the aortic content of most other elements, such as sodium, potassium, and magnesium (128). Vascular calcification linked to age is also specific for arteries and does not involve other soft tissues, such as veins (57,60,117). Vascular calcification is associated with hypertension. Blumenthal et al. (9) showed that the onset of arterial calcification occurs at an earlier age in hypertensive subjects. The association in humans between arterial calcification and hypertension has since been reported by many investigators (75). The etiology of the complex multifactorial interactions, however, between hypertension (and associated changes in vascular wall mechanics) and amplification of calcification remains obscure.Vascular calcification can occur in localized intimal plaques and in a diffuse fashion in the media (53), and often there is no indication in published reports of where samples were taken. Méndez and Tejada (76) reported that the calcium content of plaques is 10-fold higher than that of "plaque-free" artery. Thus "contamination" of samples with plaque material could mask medial, diffuse elastocalcinosis. It is to be noted that the calcium content of "normal" intima (i.e., free of plaques and fatty streaks) is low and shows only a slight increase with age (6, 29). Medial elastocalcinosis independent of atheroma-associated calcification has been demonstrated by Elliot and McGra...

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“…The outcome of VDRA therapy is difficult to predict due to the myriad of vasculotropic effects (both anti-calcific and pro-calcific) downstream of vitamin D receptor activation 25 . This complexity emphasizes the need for in vivo studies to assess the overall consequence of VDRA therapy on VC.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet

Lau

Leaf

et al. 2012

Kidney International

228

179

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Vascular calcification is common in chronic kidney disease, where cardiovascular mortality remains the leading cause of death. Patients with kidney disease are often prescribed vitamin D receptor agonists (VDRAs) that confer a survival benefit, but the underlying mechanisms remain unclear. Here we tested two VDRAs in a mouse chronic kidney disease model where dietary phosphate loading induced aortic medial calcification. Mice were given intraperitoneal calcitriol or paricalcitol three times per week for three weeks. These treatments were associated with half of the aortic calcification compared to no therapy, and there was no difference between the two agents. In the setting of a high phosphate diet, serum parathyroid hormone and calcium levels were not significantly altered by treatment. VDRA therapy was associated with increased serum and urine klotho levels, increased phosphaturia, correction of hyperphosphatemia, and lowering of serum fibroblast growth factor-23. There was no effect on elastin remodeling or inflammation, however, the expression of the anti-calcification factor, osteopontin, in aortic medial cells was increased. Paricalcitol upregulated osteopontin secretion from mouse vascular smooth muscle cells in culture. Thus, klotho and osteopontin were upregulated by VDRA therapy in chronic kidney disease, independent of changes in serum parathyroid hormone and calcium.

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Calciotropic Hormones and Arterial Physiology

Cited by 12 publications

References 41 publications

Arterial calcification and bone physiology: role of the bone–vascular axis

Arterial calcification and bone physiology: role of the bone–vascular axis

Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences

Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet

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