Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties
Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties
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DOI：
10.1161/01.res.0000259560.39234.99
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发表时间：
2007-03-02
影响因子：
20.1
通讯作者：
Houser, Steven R.
中科院分区：
文献类型：
--
作者：
Chen, Xiongwen;Wilson, Rachel M.;Houser, Steven R.
最近的研究表明，而不是终末分化，成人心脏是一个自我更新的器官，具有从心脏干/祖细胞（CS/PC）产生新的心肌细胞的能力。本研究检验了以下假设：在青少年生长期间产生新的肌细胞，以增加肌细胞数量，并且这些新形成的肌细胞最初是小的、单核的、有增殖能力的，并且具有不成熟的性质。心室肌细胞（VM）和cKit（+）（干细胞受体）CS/PC分离自11周和22周的猫心脏。分别测定溴脱氧尿苷掺入（体内）和p16（INK 4a）免疫染色以评估肌细胞细胞周期活性和衰老。端粒酶活性，收缩，Ca 2+瞬变，和电生理进行了比较，在小单核（SMMs）和大双核（LBMs）心肌细胞。在青春期，心脏质量增加了101%，但左心室肌细胞体积仅增加了77%。大多数VM为双核（87% vs 12%为单核），且大于单核肌细胞。SMMs的溴脱氧尿苷阳性率（SMMs与LBM：3.1%与0.8%; P < 0.05）和p16（INK 4a）阴性率较高，小肌细胞的端粒酶活性高于大肌细胞。收缩和Ca 2+瞬变延长SMMs与LBM和Ca 2+释放紊乱的SMMs与减少瞬态外向电流和T-小管密度。T型钙电流，通常见于胎儿/新生儿VM，被发现只在SMMs和CS/PC来源的心肌细胞。青少年心脏发育过程中肌细胞数量增加。这些新的肌细胞最初很小，功能不成熟，通常在胎儿/新生儿时期发现离子通道表达模式。
Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit(+) (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16(INK4a) immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca2+ transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P < 0.05), and p16(INK4a) negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca2+ transients were prolonged in SMMs versus LBMs and Ca2+ release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca2+ current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period.