If ACE activity is involved in the proliferative process of in-stent restenosis, plasma ACE itself may be a more direct marker of these phenomena than the ACE genotype. In fact, although plasma and cellular ACE levels are genetically controlled, the I/D polymorphism may be only a marker in linkage disequilibrium with a functional mutation located within or close to the ACE gene. Increasing evidence shows that ACE is up-regulated during the healing process that follows balloon injury of the arterial wall and that the degree of the proliferative response is correlated to the deeper damage of the vessel caused by the use of metallic prosthesis or high expansion pressures. The long-lasting ACE activity in the cells of the in-stent restenotic plaque close to the metallic wires was demonstrated, for the first time, by our group in a preliminary report; more complete results will follow in the near future. Thus the example of the ACE I/D polymorphism makes apparent the association between a genetic marker, the corresponding phenotype (represented by the low, intermediate or high plasma level of the enzyme), and the pathophysiological effect expressed in different degrees of reparative initial proliferation after vessel injury. These findings are consistent with the observation that in-stent restenosis shows a bimodal distribution; indeed patients undergoing stent implantation are distributed in two sub-populations with a different susceptibility for in-stent restenosis. This susceptibility to develop initial hyperplasia is patient-related and likely to be genetically determined. If a strong association between a genetic marker and the risk of restenosis can be found, this knowledge could be implemented in the individual treatment strategy of patients. The role of the RAS seems more important in the proliferative phenomenon of in-stent restenosis than in other cardiovascular disorders, suggesting that patients with in-stent restenosis may represent an appropriate target for studying the role of the I/D polymorphism in coronary artery disease
Relationship between plasma ACE activity and the proliferative healing process in coronary vessel injury after coronary stenting.
MATULLO, Giuseppe;PIAZZA, Alberto
2000-01-01
Abstract
If ACE activity is involved in the proliferative process of in-stent restenosis, plasma ACE itself may be a more direct marker of these phenomena than the ACE genotype. In fact, although plasma and cellular ACE levels are genetically controlled, the I/D polymorphism may be only a marker in linkage disequilibrium with a functional mutation located within or close to the ACE gene. Increasing evidence shows that ACE is up-regulated during the healing process that follows balloon injury of the arterial wall and that the degree of the proliferative response is correlated to the deeper damage of the vessel caused by the use of metallic prosthesis or high expansion pressures. The long-lasting ACE activity in the cells of the in-stent restenotic plaque close to the metallic wires was demonstrated, for the first time, by our group in a preliminary report; more complete results will follow in the near future. Thus the example of the ACE I/D polymorphism makes apparent the association between a genetic marker, the corresponding phenotype (represented by the low, intermediate or high plasma level of the enzyme), and the pathophysiological effect expressed in different degrees of reparative initial proliferation after vessel injury. These findings are consistent with the observation that in-stent restenosis shows a bimodal distribution; indeed patients undergoing stent implantation are distributed in two sub-populations with a different susceptibility for in-stent restenosis. This susceptibility to develop initial hyperplasia is patient-related and likely to be genetically determined. If a strong association between a genetic marker and the risk of restenosis can be found, this knowledge could be implemented in the individual treatment strategy of patients. The role of the RAS seems more important in the proliferative phenomenon of in-stent restenosis than in other cardiovascular disorders, suggesting that patients with in-stent restenosis may represent an appropriate target for studying the role of the I/D polymorphism in coronary artery disease
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
