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

Related Links:

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
This article summarizes recent knowledge and clinical advances in machine perfusion (MP) of thoracic organs. MP of thoracic organs has gained much attention during the last decade. Clinical studies are investigating the role of MP to preserve, resuscitate, and assess heart and lungs prior to transplantation. Currently, MP of the cardiac allograft is essential in all type DCD heart transplantation while MP of the pulmonary allograft is mandatory in uncontrolled DCD lung transplantation. MP of thoracic organs also offers an exciting platform to further investigate downregulation of the innate and adaptive immunity prior to r...
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
CONCLUSIONS: Decellularized heart valves could be the new material used as artificial heart valves. Pulmonary allografts derived from the hearts of heart transplant recipients are considered to be useful material for decellularized heart valves. The application of this valve to Japanese clinical circumstances and using the hearts of heart transplant recipients is considered to be very significant. PMID: 29657239 [PubMed - as supplied by publisher]
Source: Circulation Journal - Category: Cardiology Authors: Tags: Circ J Source Type: research
Allograft tricuspid regurgitation (TR) occurs after orthotopic heart transplantation (OHT) and is associated with significant morbidity. Prophylactic tricuspid repair with DeVega annuloplasty (DVA) of the donor heart has been reported to improve TR, renal dysfunction and mortality in cardiac transplant recipients. This is the first study to investigate the electrical and hemodynamic effects of DVA during OHT.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
More News: Biomedical Science | Bone Graft | Cardiology | Gastroschisis Repair | Heart | Heart Transplant | Transplant Surgery | Transplants