The Role of Elastin Degradation in Vascular Calcification: Possibilities to Repair Elastin and Reverse Calcification

Abstract

Vascular calcification disrupts cardiovascular hemodynamics, and it is considered as a significant risk factor for all-cause mortality and morbidity. Elastin is an essential extracellular matrix component of the healthy arteries of nearly all vertebrates. The principle function of elastic fiber is to provide elasticity to the large blood vessels, allowing reversible deformation during cyclic hemodynamic loading without energy dissipation upon load retrieval. During aging and pathology-associated vascular diseases, elastic fiber degradation is an important predictor of disease progression. Elastin fragmentation and degradation and the resulting elastin-derived peptides cause the loss of arterial cellular homeostasis and ultimately vascular calcification. A large group of research studies is succeeded to halt or limit the calcification process. However, the treatment strategies that are focused on calcification reversal, subsequent elastin regeneration, and recapitulating the healthy arterial integrity are scarce. Moreover, almost all the treatments are based on either oral or systemic drug delivery that accompanies various side effects. To address these issues, authors have developed a nanoparticle-loaded targeting drug delivery approach that targets explicitly damaged elastic fibers in diseased arteries. This targeted therapy managed to reverse already developed vascular calcification in animal models first by calcium sequestration with ethylenediaminetetraacetic acid (EDTA) delivery, followed by elastic fiber regeneration via pentagalloyl glucose (PGG) delivery. Such therapies not only reversed calcification but decreased inflammation and enzyme activities while returning vascular smooth muscle cells to the healthy phenotype.