α-Lipoic acid attenuates coxsackievirus B3-induced ectopic calcification in heart, pancreas, and lung.
Ectopic mineralization of soft tissues is known to be a typical response to systemic imbalance of various metabolic factors as well as tissue injury, leading to severe clinical consequences. In this study, coxsackievirus B3 (CVB3) infection in mice resulted in significant tissue injury, especially in the heart and pancreas. Inflammatory damage and apoptotic cell death were observed in CVB3-infected heart and pancreas tissues. Along with tissue damage, substantial ectopic calcification was detected in CVB3-infected heart, pancreas, and lung tissues, as determined by von Kossa staining and calcium content quantification. In addition, CVB3 infection induced upregulation of osteogenic signals, including six genes (BMP2, SPARC, Runx2, osteopontin, collagen type I, and osterix) in the heart, three genes (SPARC, osteopontin, and collagen type I) in the pancreas, and two genes (BMP2 and alkaline phosphatase) in the lung, as determined by quantitative real-time PCR analysis. Intriguingly, we showed that α-lipoic acid diminished CVB3-mediated inflammatory and apoptotic tissue damage, subsequently ameliorating ectopic calcification via the suppression of osteogenic signals. Collectively, our data provide evidence that ectopic calcification induced by CVB3 infection is implicated in the induction of osteogenic propensity, and α-lipoic acid may be a potential therapeutic agent to ameliorate pathologic calcification.
Department of Clinical Pathology, Taekyeung College, Gyeungsan 712-719, Republic of Korea.
Hyo Shin
HS
Kim
Hong-In
HI
Shin
Hyun-Sook
HS
Lim
Tae Yoon
TY
Lee
Kyunghee
K
Lee
Daewon
D
Jeong
D000818:Animals; D002114:Calcinosis / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D003384:Coxsackievirus Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D029822:Enterovirus B, Human; D005260:Female; D006321:Heart / Q000821:virology; D006801:Humans; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D010179:Pancreas / Q000473:pathology / Q000821:virology; D008063:Thioctic Acid / Q000627:therapeutic use*
D008063:Thioctic Acid