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1.
The heart is one of the least regenerative organs in the body, and highly vulnerable to the increasing incidence of cardiovascular diseases in an aging world population. Cell-based approaches aimed at cardiac repair have recently caused great public excitement. But clinical trials of patients’ own skeletal myoblasts or bone marrow cells for transplantation have been disappointing. Human embryonic stem cells (hESCs) form bona fide cardiomyocytes in vitro which are readily generated in mass culture and are being tested in animal models of heart damage. The early results, while encouraging, underscore that much remains to be done. This review focuses on the many challenges that remain before hESCs-mediated repair of the human heart becomes a reality. 相似文献
2.
Soumen Devidutta Chennapragada Sridevi Calambur Narasimhan 《Indian pacing and electrophysiology journal》2016,16(1):40-45
Cardiac resynchronization therapy device (CRT-P and CRT-D) implantation has increased tremendously with increasing operator experience, eligible patients and expansion of indications. Refinements in devices and algorithms now aid physicians to improve biventricular pacing and optimize CRT. We report a case in which an interesting device program was used to achieve biventricular pacing after repeated dislodgement of the atrial lead in a patient implanted with CRT-D. 相似文献
3.
Wolfram Nagel 《生物化学与生物物理学报:生物膜》1980,599(2):736-740
Inhibition by ouabain of rheogenic Na+ transport across the basolateral membranes of frog skin is found to be manifest within 3–4 min. This rate of pump inhibition is not different from the rate of diffusion through extracellular tissue layers between the serosal bath and the actual site of action, i.e., the epithelial cell layers. It is concluded that the well-known slow time course of decrease in transepithelial current flow is due ionic redistribution and conductance changes of the epithelial membranes secondary to pump inhibition. 相似文献
4.
Andrew Leask 《Journal of cell communication and signaling》2010,4(1):73-74
Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes. 相似文献
5.
Cardiac fibroblasts contribute to the structure and function of the myocardium. However their involvement in electrophysiological processes remains unclear; particularly in pathological situations when they proliferate and develop fibrosis. We have identified the connexins involved in gap junction channels between fibroblasts from adult mouse heart and characterized their functional coupling. RT-PCR and Western blotting results show that mRNA and proteins of connexin40 and connexin43 are expressed in cultured cardiac fibroblasts, while Cx45 is not detected. Analysis of gap junctional communications established by these connexins with the gap-FRAP technique demonstrates that fibroblasts are functionally coupled. The time constant of permeability, k, calculated from the fluorescence recovery curves between cell pairs is 0.066 ± 0.005 min− 1 (n = 65). Diffusion analysis of Lucifer Yellow through gap junction channels with the scrape-loading method demonstrates that when they are completely confluent, a majority of fibroblasts are coupled forming an interconnecting network over a distance of several hundred micrometers. These data show that cardiac fibroblasts express connexin40 and connexin43 which are able to establish functional communications through homo and/or heterotypic junctions to form an extensive coupled cell network. It should then be interesting to study the conditions to improve efficiency of this coupling in pathological conditions. 相似文献
6.
Fei Han Li Yin Xiao Jiang Xi Zhang Ning Zhang Juntang Yang Weiming Ouyang Xianglin Hao Wenbin Liu Yongsheng Huang Hongqiang Chen Fei Gao Zhongtai Li Qiaonan Guo Jia Cao Jinyi Liu 《Aging cell》2021,20(5)
Although important factors governing the meiosis have been reported in the embryonic ovary, meiosis in postnatal testis remains poorly understood. Herein, we first report that SRY‐box 30 (Sox30) is an age‐related and essential regulator of meiosis in the postnatal testis. Sox30‐null mice exhibited uniquely impaired testis, presenting the abnormal arrest of germ‐cell differentiation and irregular Leydig cell proliferation. In aged Sox30‐null mice, the observed testicular impairments were more severe. Furthermore, the germ‐cell arrest occurred at the stage of meiotic zygotene spermatocytes, which is strongly associated with critical regulators of meiosis (such as Cyp26b1, Stra8 and Rec8) and sex differentiation (such as Rspo1, Foxl2, Sox9, Wnt4 and Ctnnb1). Mechanistically, Sox30 can activate Stra8 and Rec8, and inhibit Cyp26b1 and Ctnnb1 by direct binding to their promoters. A different Sox30 domain required for regulating the activity of these gene promoters, providing a “fail‐safe” mechanism for Sox30 to facilitate germ‐cell differentiation. Indeed, retinoic acid levels were reduced owing to increased degradation following the elevation of Cyp26b1 in Sox30‐null testes. Re‐expression of Sox30 in Sox30‐null mice successfully restored germ‐cell meiosis, differentiation and Leydig cell proliferation. Moreover, the restoration of actual fertility appeared to improve over time. Consistently, Rec8 and Stra8 were reactivated, and Cyp26b1 and Ctnnb1 were reinhibited in the restored testes. In summary, Sox30 is necessary, sufficient and age‐associated for germ‐cell meiosis and differentiation in testes by direct regulating critical regulators. This study advances our understanding of the regulation of germ‐cell meiosis and differentiation in the postnatal testis. 相似文献
7.
J. Sherrod DeVerse Keith A. Bailey Greg A. Foster Vaishali Mittal Stuart M. Altman Scott I. Simon Anthony G. Passerini 《Journal of visualized experiments : JoVE》2012,(65)
Atherogenesis is potentiated by metabolic abnormalities that contribute to a heightened state of systemic inflammation resulting in endothelial dysfunction. However, early functional changes in endothelium that signify an individual''s level of risk are not directly assessed clinically to help guide therapeutic strategy. Moreover, the regulation of inflammation by local hemodynamics contributes to the non-random spatial distribution of atherosclerosis, but the mechanisms are difficult to delineate in vivo. We describe a lab-on-a-chip based approach to quantitatively assay metabolic perturbation of inflammatory events in human endothelial cells (EC) and monocytes under precise flow conditions. Standard methods of soft lithography are used to microfabricate vascular mimetic microfluidic chambers (VMMC), which are bound directly to cultured EC monolayers.1 These devices have the advantage of using small volumes of reagents while providing a platform for directly imaging the inflammatory events at the membrane of EC exposed to a well-defined shear field. We have successfully applied these devices to investigate cytokine-,2 lipid-3, 4 and RAGE-induced5 inflammation in human aortic EC (HAEC). Here we document the use of the VMMC to assay monocytic cell (THP-1) rolling and arrest on HAEC monolayers that are conditioned under differential shear characteristics and activated by the inflammatory cytokine TNF-α. Studies such as these are providing mechanistic insight into atherosusceptibility under metabolic risk factors. 相似文献
8.
9.
Nitric oxide synthase (NOS) may be uncoupled to produce superoxide rather than nitric oxide (NO) under pathological conditions such as diabetes mellitus and insulin resistance, leading to cardiac contractile anomalies. Nonetheless, the role of NOS uncoupling in insulin resistance-induced cardiac dysfunction remains elusive. Given that folic acid may produce beneficial effects for cardiac insufficiency partially through its NOS recoupling capacity, this study was designed to evaluate the effect of folic acid on insulin resistance-induced cardiac contractile dysfunction in a sucrose-induced insulin resistance model. Mice were fed a sucrose or starch diet for 8 weeks before administration of folic acid in drinking water for an additional 4 weeks. Cardiomyocyte contractile and Ca2+ transient properties were evaluated and myocardial function was assessed using echocardiography. Our results revealed whole body insulin resistance after sucrose feeding associated with diminished NO production, elevated peroxynitrite (ONOO−) levels, and impaired echocardiographic and cardiomyocyte function along with a leaky ryanodine receptor (RYR) and intracellular Ca2+ handling derangement. Western blot analysis showed that insulin resistance significantly promoted Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation, which might be responsible for the leaky RYR and cardiac mechanical dysfunction. NOS recoupling using folic acid reversed insulin resistance-induced changes in NO and ONOO−, CaMKII phosphorylation, and cardiac mechanical abnormalities. Taken together, these data demonstrated that treatment with folic acid may reverse cardiac contractile and intracellular Ca2+ anomalies through ablation of CaMKII phosphorylation and RYR Ca2+ leak. 相似文献
10.
A nonpulsatile perfusion apparatus, based on the air-lift pump principle, has been developed. Circulation of the perfusate, as well as oxygenation and maintenance of acid-base balance, is provided by the flow of a mixture of 97% oxygen and 3% carbon dioxide. The system is easily and entirely portable. Eleven baboons underwent orthotopic allotransplantation with donor hearts stored by continuous hypothermic (4-10 degrees C) perfusion for periods of up to 24 hr. Three were electively killed after 2 to 3 days; the remaining eight, immunosuppressed with methylprednisolone and either azathioprine or cyclosporin A, survived to rejection at between 10 and 49 days. Cardiac catheterization performed in six animals 7-14 days after allotransplantation showed virtually normal hemodynamic data. Three more baboons underwent heart excision and storage by hypothermic perfusion for 24 hr, and subsequent othotopic autotransplantation, the circulation of the baboon being maintained in the interim by an allograft. One animal survives 8 months later with hemodynamic data at cardiac catheterization differing little from that obtained before autotransplantation. This perfusion system has subsequently been used to store four human donor hearts prior to heterotopic transplantation. 相似文献