腎と骨代謝 Vol.32 No.4(6)


特集名 軟部組織の石灰化 ─ 血管と心臓弁
題名 血管石灰化と心臓弁石灰化に関与する分子とその働き
発刊年月 2019年 10月
著者 倉林 正彦 群馬大学大学院医学系研究科循環器内科学
【 要旨 】 血管石灰化は,心不全や急性冠症候群などの心血管リスクと関連し,臨床的意義は非常に大きいが,未だ有効な治療法や予防法はない.最近までに,多くの石灰化促進因子や抑制因子が同定され,それらを積み込む細胞外小胞(EV;extracellular vesicle)の役割,および石灰化を促進するEVの生成におけるsortilinの役割が示され,新たな治療標的として期待されている.また,大動脈弁の石灰化の原因としてlipoprotein(a)〔Lp(a)〕が注目されている.LDL-C低下療法においては有意な石灰化抑制効果は得られないのに対して,Lp(a)を低下させることで大動脈弁石灰化,そして大動脈弁狭窄症の進行を抑制できるかの研究が進められている.
Theme Ectopic calcification on soft tissue: Vascular calcification and cardiac valvular calcification
Title Molecular mechanism of vascular calcification and valvular calcification
Author Masahiko Kurabayashi Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine
[ Summary ] Vascular calcification and aortic valve disease are prevalent disorders that affect patients with diabetes, metabolic syndrome, chronic kidney disease and aged individuals. Recent studies identified a specific trafficking protein, sortilin, as a key player in the formation of calcifying extracellular vesicles secreted by vascular smooth muscle cells. In addition, elevated Lp(a) has been shown to be a risk factor for aortic stenosis (AS), and a recent genomewide association study (GWAS) showed that the singlenucleotide polymorphisms within the LPA gene were associated with highly elevated Lp(a) levels and with aortic valve calcification. Hypotheses have been proposed that accumulation of oxidized phospholipids (oxPL) as well as apolipoproteins(a) within the intima and valvular tissue contribute to the vascular calcification. Future studies to evaluate whether lowering sortilin or Lp(a) levels will reduce the incidence or progression of AS is warranted
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