New Aspects of Vascular Calcification: Histone Deacetylases and Beyond

Abstract

Vascular calcification is a pathologic phenomenon in which calcium phosphate is ectopically deposited in the arteries. Previously, calcification was considered to be a passive process in response to metabolic diseases, vascular or valvular diseases, or even aging. However, now calcification is recognized as a highly-regulated consequence, like bone formation, and many clinical trials have been carried out to elucidate the correlation between vascular calcification and cardiovascular events and mortality. As a result, vascular calcification has been implicated as an independent risk factor in cardiovascular diseases. Many molecules are now known to be actively associated with this process. Recently, our laboratory found that posttranslational modification of histone deacetylase (HDAC) 1 is actively involved in the development of vascular calcification. In addition, we found that modulation of the activity of HDAC as well as its protein stability by MDM2, an HDAC1-E3 ligase, may be a therapeutic target in vascular calcification. In the present review, we overview the pathomechanism of vascular calcification and the involvement of posttranslational modification of epigenetic regulators.

Vascular Calcification—New Insights into Its Mechanism

“…In addition, it is known that vascular calcification affects intracellular signaling, due to epigenetic phenomena, including altered microRNA levels, DNA methylation, and histone modifications. In addition, aging affects calcification through osteoinductive signaling, inflammatory cytokines, and oxidative stress [78,[81][82][83][84][85]. Moreover, cellular phenomena that affect osteoinductive intracellular signaling, via hyperphosphatemia, include autophagy, ER stress, and mitochondrial dysfunction.…”

Aortic calcification in patients with rheumatoid arthritis and ankylosing spondylitis: a cross-sectional case-control study

“…Vascular calcification is a pathological process of calcium and phosphate salts accumulation within the arterial wall. It involves mainly two forms, intimal calcification in atherosclerosis and cardiac valve calcification, and artery tunica media calcification (also known as Mönckeberg sclerosis) in aging, diabetes mellitus, and chronic kidney disease mediated calcification, with various degrees overlap of them [13,14]. Vascular medial calcification increases vascular wall hardness and reducing vascular compliance.…”

The potential role of miRNAs in calcification of cardiovascular diseases

“…Кальциноз ССС представляет собой патологическое накопление фосфатов кальция в медиальных и интимальных слоях сосудистых стенок. Его развитие зачастую ассоциировано с метаболическими возраст-зависимыми заболеваниями, такими как хроническая почечная недостаточность, диабет II типа и атеросклероз [23,24].…”

“…Первый тип -кальциноз интимы, связанный с развитием атеросклеротической бляшки, в частности, с отложением липидов и кристаллов холестерина под поврежденным эндотелием. Второй тип -кальциноз медии, также известный как артериосклероз Менкеберга, который характеризуется отложением солей кальция в слоях гладкой мускулатуры сосудов [24,25].…”