Myocardial protection against reperfusion injury: the cGMP pathway.
Reperfusion injury may cause myocardial cell death and limit the benefit achieved by restoration of coronary artery patency in patients with acute myocardial infarction. The mechanism includes altered Ca(2+) handling with cytosolic and mitochondrial Ca(2+) overload, Ca(2+)- and ATP-dependent hypercontraction, cytoskeletal fragility, mitochondrial permeability transition and gap junction-mediated propagation of cell death, as well as alterations in non-cardiomyocyte cells, in particular platelets and endothelial cells. cGMP modulates favorably all these mechanism, mainly through PKG-mediated actions, but cGMP synthesis is altered in reperfused cardiomyocytes and endothelial cells by mechanisms that are only partially understood. Stimulation of cGMP synthesis during initial reperfusion by means of natriuretic peptides has been found protective in different animal models and in patients. Moreover, increasing evidence indicates that cGMP is an important step in signal transduction of endogenous cardioprotection. Thus, the cGMP pathway appears as a key element in the pathophysiology of myocardial ischaemia-reperfusion and as a promising therapeutic target in patients with acute myocardial infarction.
Laboratorio de Cardiología Experimental, Area del Cor, Hospital Universitari Vall d'Hebron, Barcelona, Spain. dgdorado@vhebron.net
David
D
Garcia-Dorado
Luis
L
Agulló
Carmem Lluisa
CL
Sartorio
Marisol
M
Ruiz-Meana
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D015290:Second Messenger Systems / Q000187:drug effects*; D013997:Time Factors
D002317:Cardiovascular Agents; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP