Investigational Pharmacological Treatments for Vascular Calcification

Abstract

In the past decade, significant progress has been made in understanding the medical threats posed by vascular calcification (VC). This recent development comes after a long history of misinterpreting this condition as a mere consequence of aging. As a result, there is presently no pharmacological treatment approved for the prevention or ablation of VC. Patients diagnosed with this chronic and debilitating condition are hence left at a great risk of experiencing serious cardiovascular events. Researchers, however, are ever better understanding the disease's pathophysiology, and promising avenues for drug development have emerged. In this review, recent clinical results of proposed calcification inhibitors are consolidated and selected investigational therapeutics are portrayed. Finally, opportunities for drug development approaches are highlighted and an objective account of challenges that remain in achieving this goal is provided.

Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers

“…Most drug candidates currently under clinical investigation for VC (e.g., bisphosphonates, phosphate-binders, vitamin K, or magnesium) act by correcting the imbalance of calcification promoters (i.e., hyperphosphatemia) and inhibitors in VC-affected individuals. However, these drug candidates have yet to prove their efficacy in cardiovascular disease patients 17,18 .…”

Uremic Toxins and Vascular Calcification–Missing the Forest for All the Trees

“…Although there is currently no approved therapy to stop, attenuate or regress VC there are several appealing approaches [ 294 , 295 ]. These may be categorized as: (1) direct pharmacological inhibition of hydroxyapatite (HA) growth, (2) increasing level or activity of anti-calcifying factors, (3) reducing pro-calcifying factors.…”

“…This carboxylation is pivotal to activate the endogenous VC inhibitor matrix Gla-protein (MGP) [ 297 ]. Several clinical trials are currently underway to examine the potential of vitamin K supplementation to hold or reduce VC [ 294 ]. Additionally, also certain URM can be protective against VC ( Table 2 , Table 3 and Table 4 ), yet this has not been studied in detail.…”

Pathophysiological and Genetic Aspects of Vascular Calcification

“…Intimal calcification is associated with atherosclerotic plaque formation comprises fibrous cap, necrotic/lipid nucleus, cholesterol crystals, inflammatory cells that are prone to erosion, rupture and obstruction of blood flow, reduced organ perfusion, and ischemic syndromes [5,6].…”

“…It can cause stiffness of the vascular wall, leading to changed arterial hemodynamic properties. is results in an increased chance of hypertension and left ventricular hypertrophy and aggravates the risk of cardiac events [5,6].…”