Hiromi Kayamori

Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade

Vascular cells have a finite lifespan and eventually enter irreversible growth arrest called cellular senescence. We have previously suggested that vascular cell senescence contributes to the pathogenesis of human atherosclerosis. Amlodipine is a mixture of two enantiomers, one of which (S- enantiomer) has L-type channel blocking activity, while the other (R+ enantiomer) shows ~1000-fold weaker channel blocking activity than S- enantiomer and has other unknown effects. It has been reported that amlodipine inhibits the progression of atherosclerosis in humans, but the molecular mechanism of this beneficial effect remains unknown. Apolipoprotein E-deficient mice on a high-fat diet were treated with amlodipine, its R+ enantiomer or vehicle for eight weeks. Compared with vehicle treatment, both amlodipine and the R+ enantiomer significantly reduced the number of senescent vascular cells and inhibited plaque formation to a similar extent. Expression of the pro-inflammatory molecule interleukin-1β was markedly upregulated in vehicle-treated mice, but was inhibited to a similar extent by treatment with amlodipine or the R+ enantiomer. Likewise, activation of p53 (a critical inducer of senescence) was markedly suppressed by treatment with amlodipine or the R+ enantiomer. These results suggest that amlodipine inhibits vascular cell senescence and protects against atherogenesis at least partly by a mechanism that is independent of calcium channel blockade.

Bidirectional Shunt Trajectory in Ventricular Septal Defect With Eisenmenger’s Syndrome

Received March 19, 2018; revised manuscript received April 13, 2018; accepted April 18, 2018; released online May 25, 2018 Time for primary review: 23 days Department of Cardiovascular Biology and Medicine (H.K., T. Kashimura, N.K., Y.I., T.T., T. Okubo, M.H., T.Y., T. Ozawa, K.O., T.M.), Department of Advanced Cardiopulmonary Vascular Therapeutics (T. Kashimura, M.H.), Department of Radiology (Y.H., T. Kanazawa), Niigata University Graduate School of Medical and Dental Sciences, Niigata; Division of Cardiology, Nagaoka Red-Cross Hospital, Nagaoka (T.F.), Japan Mailing address: Takeshi Kashimura, MD, PhD, Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-754 Asahimachi, Niigata 951-8510, Japan. E-mail: kashi@med.niigata-u.ac.jp ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp Bidirectional Shunt Trajectory in Ventricular Septal Defect With Eisenmenger’s Syndrome