Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Δημόπουλος Μελέτιος Αθανάσιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μητράκου Φαναριώτου Ασημίνα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Βλαχόπουλος Χαράλαμπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σταματελόπουλος Κίμων, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πρωτόγερου Αθανάσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μανιός Ευστάθιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γαβριατοπούλου Μαρία, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Συσχέτιση δεικτών αγγειακής φλεγμονής με την παρουσία και την πρόοδο της υποκλινικής αθηρωμάτωσης σε ασθενείς με στεφανιαία νόσο
Translated title:
Correlation of markers of vascular inflammation with the presence and the acceleration of subclinical atherosclerosis in patients with coronary heart disease
Summary:
Background
The central role of of cathepsin B (CTSB) and cathepsin S (CTSS) in ageing processes, atherogenesis and atherosclerotic plaque rupture, is supported by experimental evidence, but the clinical significance of its involvement in early stages of atherosclerotic heart disease and in vascular aging is still unknown. We aimed to assess the association of CTSB and CTSS expression levels with vascular aging and atherosclerosis in humans.
Methods
CTSB and CTSS expression in peripheral blood mononuclear cells (PBMCs) was measured in 249 consecutive subjects [162 without clinically overt coronary artery disease (CAD), 51 with stable CAD and 36 with acute myocardial infarction (AMI)]. Participants underwent peripheral vascular assessment by measurement of aortic hemodynamics, pulse wave velocity (PWV) as marker of arterials stifness and vascular aging and by carotid and femoral ultrasound appreciating the presence and extension of subclinical peripheral arterial disease. A random sample of the population (n=100) was reevaluated 3 years after first examination. Patients were monitored for cardiovascular events, and as the final outcome was determined death of all causes, AMI and revascularization of coronary artery.
Results
Non-CAD subjects in the highest tertile of CTSB presented 4-fold increased odds for higher PWV (OR=4.38, 1.20-15.9, p=0.025) after risk adjustment for traditional CAD factors and renal function. CTSS presented similar association but statistical significance was lost after multifactorial adjustment.(p=0.084). CTSB (p=0.006) and CTSS (p<0.001) expression was increased in patients with CAD compared to population without clinically overt CAD. CTSS expression was also increased in stable CAD group compared to controls (p=0.036). CTSB (p=0.048) and CTSS (p=0.026) increased levels were independently associated with the number of diseased coronary arteries after adjustment for risk factors and renal function. In the total cohort, increased CTSB expression, but not CTSS expression, was associated with the number of diseased arterial beds (subclinical or clinical presence of lession in carotid and femoral arteries, in aorta and in coronary arteries, adjusted OR=1.60,1.05-2.43, for highest versus lower textiles, p=0.029) after adjustment for risk factors, renal function and presence of CAD. In a subgroup of population that was examined after 3 years, increased CTSS expression, but not CTSB, during first visit, was associated with increased progression of arterial stifness during follow up (p<0.05 for group interaction of CTSS). Finally, increased CTSB expression ( 3rd tertile) was associated with increased risk of future cardiovascular events (adjusted HR 3.88, 95%CI 1.43-10.53, p=0.008).
Conclusion
Increased CTSB and CTSS expression is associated with aortic stiffness, subclinical and clinical atherosclerotic disease. Moreover increased CTSS expression was associated with accelarated arterial stifening. These findings suggest a mechanistic role of CTSB and CTSS in accelerating vascular aging and atherosclerosis and future studies should elucidate the potential role of cathepsins as biomarkers in cardiovascular disease.
Main subject category:
Health Sciences
Keywords:
Cathepsin, Atherosclerosis, Coronary disease
Number of references:
330
