Nitric oxide and the enigma of cardiac hypertrophy.
In pathological conditions associated with persistent increases in hemodynamic workload (old myocardial infarction, high blood pressure, valvular heart disease), a number of signalling pathways are activated in the heart, all of which promote hypertrophic growth of the heart, characterised at the cellular level by increases in individual cardiac myocyte size. Some of these pathways are required for a successful adaptation to cardiac injury. Other pathways are maladaptive, however, as they lead to progressive contractile dysfunction and heart failure. The free radical gas nitric oxide and natriuretic peptides, both of which are produced in the heart, have emerged as endogenous inhibitors of maladaptive hypertrophy signalling. Overall, it appears that cardiac hypertrophy is controlled by an interplay of pro- and antihypertrophic signalling networks. This delicate balance can tip towards adaptation or heart failure. In the future, patients living with cardiac disease may benefit from therapeutic strategies targeting maladaptive hypertrophy signalling pathways.
Kempf
Tibor
T
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Wollert
Kai C
KC
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D008954:Models, Biological; D045265:Natriuretic Peptides / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction
D045265:Natriuretic Peptides; D009569:Nitric Oxide; D019703:Calcineurin; D006152:Cyclic GMP