Zhen-Ao Zhao1,2, Xinglong Han1,2, Wei Lei1,2, Jingjing Li1,2, Zhuangzhuang Yang1, Jie Wu1, Mengchao Yao3, Xing-Ai Lu1, Lingjuan He4, Yihuan Chen1,2, Bin Zhou4, Shijun Hu1,2. 1. From the Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College (Z.-A.Z., X.H., W.L., J.L., Z.Y., J.W., X.-A.L., Y.C., S.H.), Soochow University, Suzhou, China. 2. Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Medical College (Z.-A.Z., X.H., W.L., J.L., Y.C., S.H.), Soochow University, Suzhou, China. 3. School of Life Science, Shanghai University, China (M.Y.). 4. the State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences (L.H., B.Z.).
Abstract
RATIONALE: Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited. OBJECTIVE: In this study, we tested whether the CDCs isolated from neonatal mice could benefit cardiac function in aging mice. METHODS AND RESULTS: We evaluated cardiac function of PBS- (n=15) and CDC-injected (n=19) aging mice. Echocardiography indicated that left ventricular (LV) ejection fraction (57.46%±3.57% versus 57.86%±2.44%) and LV fraction shortening (30.67%±2.41% versus 30.51%±1.78%) showed similar values in PBS- and CDC-injected mice. The diastolic wall thickness of LV was significantly increased after CDC injection, resulting in reduced diastolic LV volume. The pulse-wave Doppler and tissue Doppler imaging indicated that aging mice receiving PBS or CDC injection presented similar values of the peak early transmitral flow velocity, the peak late transmitral flow velocity, the ratio of the peak early transmitral flow velocity to the peak late transmitral flow velocity, and the ratio of the peak early transmitral flow velocity to the peak early diastolic mitral annular velocity, respectively. Pressure-volume loop experiment indicated that the LV end-diastolic pressure-volume relationship and end-systolic pressure-volume relationship were comparable in both PBS- and CDC-injected mice. Postmortem analysis of aging mouse hearts showed similar fibrotic degree in the 2 groups. In addition, the aging markers showed comparable expression levels in both PBS- and CDC-injected mice. The systemic aging performance measures, including exercise capacity, hair regrowth capacity, and inflammation, showed no significant improvement in CDC-injected mice. Finally, the telomere length was comparable between PBS- and CDC-injected mice. CONCLUSIONS: Together, these results indicate that CDCs do not improve heart function and systemic performances in aging mice.
RATIONALE: Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited. OBJECTIVE: In this study, we tested whether the CDCs isolated from neonatal mice could benefit cardiac function in aging mice. METHODS AND RESULTS: We evaluated cardiac function of PBS- (n=15) and CDC-injected (n=19) aging mice. Echocardiography indicated that left ventricular (LV) ejection fraction (57.46%±3.57% versus 57.86%±2.44%) and LV fraction shortening (30.67%±2.41% versus 30.51%±1.78%) showed similar values in PBS- and CDC-injected mice. The diastolic wall thickness of LV was significantly increased after CDC injection, resulting in reduced diastolic LV volume. The pulse-wave Doppler and tissue Doppler imaging indicated that aging mice receiving PBS or CDC injection presented similar values of the peak early transmitral flow velocity, the peak late transmitral flow velocity, the ratio of the peak early transmitral flow velocity to the peak late transmitral flow velocity, and the ratio of the peak early transmitral flow velocity to the peak early diastolic mitral annular velocity, respectively. Pressure-volume loop experiment indicated that the LV end-diastolic pressure-volume relationship and end-systolic pressure-volume relationship were comparable in both PBS- and CDC-injected mice. Postmortem analysis of aging mouse hearts showed similar fibrotic degree in the 2 groups. In addition, the aging markers showed comparable expression levels in both PBS- and CDC-injected mice. The systemic aging performance measures, including exercise capacity, hair regrowth capacity, and inflammation, showed no significant improvement in CDC-injected mice. Finally, the telomere length was comparable between PBS- and CDC-injected mice. CONCLUSIONS: Together, these results indicate that CDCs do not improve heart function and systemic performances in aging mice.
Authors: Lilian Grigorian Shamagian; Rosalinda Madonna; Doris Taylor; Andreu M Climent; Felipe Prosper; Luis Bras-Rosario; Antoni Bayes-Genis; Péter Ferdinandy; Francisco Fernández-Avilés; Juan Carlos Izpisua Belmonte; Valentin Fuster; Roberto Bolli Journal: Circ Res Date: 2019-03-15 Impact factor: 17.367