Apelin directs endothelial cell differentiation and vascular repair following immune-mediated injury

Sustained, indolent immune injury of the vasculature of a heart transplant limits long-term graft and recipient survival. This injury is mitigated by a poorly characterized, maladaptive repair response. Vascular endothelial cells respond to proangiogenic cues in the embryo by differentiation to specialized phenotypes, associated with expression of apelin. In the adult, the role of developmental proangiogenic cues in repair of the established vasculature is largely unknown. We found that human and minor histocompatibility–mismatched donor mouse heart allografts with alloimmune-mediated vasculopathy upregulated expression of apelin in arteries and myocardial microvessels. In vivo, loss of donor heart expression of apelin facilitated graft immune cell infiltration, blunted vascular repair, and worsened occlusive vasculopathy in mice. In vitro, an apelin receptor agonist analog elicited endothelial nitric oxide synthase activation to promote endothelial monolayer wound repair, and reduce immune cell adhesion. Thus, apelin acted as an autocrine growth cue to sustain vascular repair and mitigate the effects of immune injury. Treatment with an apelin receptor agonist after vasculopathy was established markedly reduced progression of arterial occlusion in mice. Together, these initial data identify proangiogenic apelin as a key mediator of coronary vascular repair and a pharmacotherapeutic target for immune-mediated injury of the coronary vasculature.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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In conclusion, using a large cohort with rich health and DNA methylation data, we provide the first comparison of six major epigenetic measures of biological ageing with respect to their associations with leading causes of mortality and disease burden. DNAm GrimAge outperformed the other measures in its associations with disease data and associated clinical traits. This may suggest that predicting mortality, rather than age or homeostatic characteristics, may be more informative for common disease prediction. Thus, proteomic-based methods (as utilised by DNAm GrimAge) using large, physiologically diverse protein sets for p...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSION: The future of organ bioengineering relies on furthering understanding of organogenesis, in vivo regeneration, regenerative immunology and long-term monitoring of implanted bioengineered organs. PMID: 32463143 [PubMed - in process]
Source: The British Journal of Surgery - Category: Surgery Authors: Tags: Br J Surg Source Type: research
This study aims to elucidate the efficacy of DPP4i in clinical LTx, and to search for a new biomarker for CLAD or overall survival (OS).
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (141) Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: Mesenchymal stem cell transplantation could be use as a potential treatment for PHLF. Introduction Partial hepatectomy is an important treatment for benign and malignant liver diseases. Although the liver can be completely regenerated after partial excision or injury, at least 1/3 of the liver should be retained in most of the patients, and 40–50% should be retained in patients with parenchymal liver disease (Adams et al., 2013; Cieslak et al., 2014). Postoperative complications, such as acute post-hepatectomy liver failure (PHLF) or small liver syndrome, may occur when the scope of excision is to...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Publication date: December 2018Source: Canadian Journal of Cardiology, Volume 34, Issue 12Author(s): Frank Battaglia, Lisa Mielniczuk, Vincent ChanAbstractWe provide an update on Canada’s first neonatal heart transplant recipient who, after cardiac retransplantation, underwent a mitral valve replacement and tricuspid valve repair. Twenty-seven years after his initial heart surgery and 13 years after his most recent transplant, this patient developed heart failure with severe mitral regurgitation secondary to a calcified mitral valve. The patient was highly sensitized with no evidence of allograft rejection; therefore...
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
Publication date: Available online 29 September 2018Source: Canadian Journal of CardiologyAuthor(s): Frank Battaglia, Lisa Mielniczuk, Vincent ChanAbstractWe provide an update on Canada’s first neonatal heart transplant recipient, who, following cardiac re-transplantation, underwent a mitral valve replacement and tricuspid valve repair. Twenty-seven years after his initial heart surgery, and thirteen years following his most recent transplant, this patient developed heart failure with severe mitral regurgitation secondary to a calcified mitral valve. The patient was highly sensitized with no evidence of allograft rej...
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
AbstractA 6-month-old infant with a double outlet right ventricle, doubly committed ventricular septal defect, and right ventricle outflow tract (RVOT) stenosis underwent intracardiac repair with RVOT reconstruction using a fresh decellularized allograft derived from a 1-year-old heart transplant recipient in Japan. Early postoperative evaluation via echocardiography and cardiac magnetic resonance imaging revealed that the pulmonary allograft and cardiac function were stable. This is the first case report on using a decellularized heart valve, which was resected from a heart transplant recipient, for primary repair of cong...
Source: General Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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