Three-year outcomes related to coronary stenting; a registry-based real-life population study.

Objectives. Developments in medication and coronary interventions have improved coronary artery disease (CAD) treatment. We studied long-term outcomes in an observational, real-life population of CAD patients undergoing percutaneous coronary intervention (PCI) depending on the presentation and the stent type used. Design and results. Register included 789 consecutive patients undergoing PCI. Follow up period was three years with primary composite outcome (MACE) of all cause -mortality, myocardial infarction and target lesion revascularization. Mean age was 65 ± 11 and 69% were male. New-generation drug-eluting stents (DES-2) were associated with lower adjusted rates of MACE (HR 0.47; 95% CI 0.29-0.77) but not mortality (HR 0.50; 95% CI 0.22-1.14) in comparison to bare-metal stents. Patients with STEMI (14.4%) or NSTEMI (13.7%) had higher crude mortality rates than those with unstable (4.5%) or stable CAD (3.1%; p < .001). The association diminished after adjustments in NSTEMI (HR 2.01; 95% CI 0.88-4.58). Among smokers 45% quitted and 36% achieved recommended cholesterol levels. Conclusions. The overall prognosis was good. Irrespective of comorbidities, NSTEMI was not associated with worse outcome than stable CAD. DES-2 was associated with lower rates of MACE than BMS without affecting mortality rate. Patients succeeded better in smoking cessation than reaching recommended cholesterol levels.

Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1.

The function of the plasma membrane calmodulin-dependent calcium ATPase (PMCA) in myocardium is unknown. PMCA is localized in caveolae, 50- to 100-nm membrane invaginations, which also contain receptors for endothelin-1 (ET-1) and various other ligands. PMCA has been suggested to play a role in regulation of caveolar signal transduction. We studied the effects of the hypertrophic agonist ET-1 and increased coronary perfusion pressure on cardiac synthesis of B-type natriuretic peptide (BNP) in transgenic rats overexpressing the human PMCA 4CI in isolated perfused heart preparation. ET-1 infusion for 2 h increased BNP mRNA levels twofold in left ventricles (LV) of nontransgenic rats, whereas no increase was noted in PMCA rat hearts. Similar responses were seen in adrenomedullin and c-fos mRNA levels, and in immunoreactive BNP secretion. Increased mechanical load produced by elevated perfusion pressure induced similar 1.5- to 1.6-fold increases in LV BNP mRNA in both nontransgenic and PMCA rat hearts. These results show that cardiac overexpression of PMCA attenuates ET-1-stimulated early induction of cardiac gene expression, suggesting that PMCA may modulate myocardial growth responses.

AM reverses pressor response to ET-1 independently of NO in rat coronary circulation.

Endothelin-1 (ET-1) elicits a vasoconstrictor response via ET(A) receptors, whereas simultaneous activation of ET(B) receptors triggers the release of nitric oxide (NO), which may limit the constrictor effect of ET-1. Recently, stimulation of ET(B) receptors has been shown to increase the secretion of adrenomedullin (AM), a newly identified vasorelaxing peptide. The present study was designed to see whether AM can oppose the vasoconstrictor response to ET-1. In the isolated perfused paced rat heart preparation, infusion of ET-1 at concentrations of 1 nmol/l for 30 min induced a significant coronary vasoconstriction, whereas it had no effect on perfusion pressure at a dose of 0.08 nmol/l. N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/l), a potent inhibitor of NO synthase (NOS), did not change the perfusion pressure when added alone to the perfusion fluid but it unmasked the constrictor effect of ET-1 at both concentrations. In the presence of L-NAME, AM (0.03 to 1 nmol/l) markedly reversed the pressor response to ET-1 at both concentrations. Administration of AM (0.03 and 1 nmol/l) alone resulted in a dose-dependent decrease in perfusion pressure, which was not modified in the presence of L-NAME. In conclusion, the coronary vasoconstrictor response to ET-1 is markedly augmented in the presence of a NOS inhibitor. This constrictor response is substantially reversed by AM. Our results indicate that AM may serve as a paracrine modulator of ET-1-induced vasoconstriction independently of the NO pathway.

Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice.

Type XV collagen occurs widely in the basement membrane zones of tissues, but its function is unknown. To understand the biological role of this protein, a null mutation in the Col15a1 gene was introduced into the germ line of mice. Despite the complete lack of type XV collagen, the mutant mice developed and reproduced normally, and they were indistinguishable from their wild-type littermates. However, Col15a1-deficient mice showed progressive histological changes characteristic for muscular diseases after 3 months of age, and they were more vulnerable than controls to exercise-induced muscle injury. Despite the antiangiogenic role of type XV collagen-derived endostatin, the development of the vasculature appeared normal in the null mice. Nevertheless, ultrastructural analyses revealed collapsed capillaries and endothelial cell degeneration in the heart and skeletal muscle. Furthermore, perfused hearts showed a diminished inotropic response, and exercise resulted in cardiac injury, changes that mimic early or mild heart disease. Thus, type XV collagen appears to function as a structural component needed to stabilize skeletal muscle cells and microvessels.