Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death.
Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response.
VCU Pauley Heart Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. Stefano.Toldo@vcuhealth.org.|Department of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA. Stefano.Toldo@vcuhealth.org.|VCU Johnson Research Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Stefano.Toldo@vcuhealth.org.
Stefano
S
Toldo
Department of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA. Mohammed.Quader@vcuhealth.org.
Mohammed
M
Quader
VCU Pauley Heart Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. Fadi.Salloum@vcuhealth.org.
Fadi N
FN
Salloum
VCU Johnson Research Center, Virginia Commonwealth University, Richmond, VA 23298, USA. emezzaroma@vcu.edu.|Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA. emezzaroma@vcu.edu.
Eleonora
E
Mezzaroma
VCU Pauley Heart Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. Antonio.Abbate@vcuhealth.org.|VCU Johnson Research Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Antonio.Abbate@vcuhealth.org.
Antonio
A
Abbate
D000818:Animals; D003643:Death; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006789:Host vs Graft Reaction / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D009927:Tissue and Organ Procurement / Q000379:methods* / Q000592:standards
Toll-like receptors; donation after brain death (DBD); donation after cardiac death (DCD); graft failure; heart transplantation; inflammasome; innate immune response; ischemia-reperfusion injury; rejection