[Psychopathological disorders and coronary diseases]. / Troubles psychopathologiques et coronaropathies.

The role of psychological factors in the genesis of coronary diseases has been considered for a long time. Friedman took it upon himself to describe a personality profile (pattern A) constituting a risk factor for coronary heart disease of which, however, the practical interest seems limited. The association of psychopathological conditions and coronary heart disease has on the other hand not been extensively studied. Recent epidemiological data show that anxiety and depressive states represent a high comorbidity with coronary heart diseases. Panic attacks remain underestimated; they seem to participate in a complex physiopathological mechanism along with ischemic coronary heart diseases. Recent studies have shown that the existence of a depressive illness during coronary heart disease and particularly in the time period following a myocardial infarction, constitutes an independent risk factor, thus increasing the mortality rate. The evolution of coronary heart disease seems greatly influenced by the existence of anxious or depressive states, the diagnosis and the treatment of these states represent a major interest towards a better management of coronary patients.

Homocysteine-thiolactone induces caspase-independent vascular endothelial cell death with apoptotic features.

OBJECTIVE: Cell death is generally classified into two large categories: apoptosis, which represents active, physiological programmed cell death, and necrosis, which represents passive cell death without underlying regulatory mechanisms. Apoptosis plays an important role in tissue homeostasis and its role in endothelium integrity can be influenced by the functional status of endothelial cells. Homocysteine, a sulfated amino-acid product of methionine demethylation, is an independent risk factor for vascular disease (arterial and venous thombosis). Our goal was to investigate the thiol-derivatives effect on the endothelial cell apoptosis. METHODS: Three parameters were measured: mitochondrial membrane potential using DiOC6(3) as the probe, DEVDase activation, and phosphatidylserine exposure on the cell surface with fluorosceinated annexin V labeling which allows apoptosis to be distinguished from necrosis. RESULTS: Homocysteine-thiolactone induced endothelial cell apoptosis in a concentration-dependent manner (range: 50-200 microM), independently of the caspase pathway. Only homocysteine-thiolactone, among the thiol derivatives tested, induced apoptosis. Apoptosis was not influenced by the serum concentration in culture medium, suggesting that the observed apoptotic process could occur in vivo. None of the inhibitors used (e.g., leupeptin, fumosinin B1, catalase, or z-VAD-fmk) was able to prevent homocysteine-induced apoptosis of vascular endothelial cells. CONCLUSION: The apoptosis of vascular endothelial cells induced by high concentration of homocysteine-thiolactone might be one step atherosclerotic cardiovascular disease, and contribute to its complication.