Accelerated arterial stiffening and gene expression profile of the aorta in patients with coronary artery disease.

BACKGROUND: Hypertension and chronic renal failure (CRF) are considered models of accelerated arterial stiffening. Arterial stiffness increases further when CRF is associated with hypertension. We hypothesized that, in patients with mild CRF, aortic gene expression profile would include genes involved in arterial calcifications and enlargement. METHOD: We analysed human aorta with the 'GeneChip Microarray' technology, in patients with or without CRF, scheduled for a coronary artery bypass graft. RESULTS: Nine of 25 patients had high-quality RNA and were included in the study. Among the 101 transcripts differentially expressed between CRF patients and controls, 97 transcripts were overexpressed in CRF patients. Two genes had the highest overexpression in CRF patients: lumican (LUM), involved in the regulation of collagen fibrillogenesis; and ornithine decarboxylase (ODC1), involved in polyamine biosynthesis, smooth muscle cell growth and proliferation. Immunohistochemical staining revealed an increased amount of LUM and ODC1 in the vascular smooth muscle cells (VSMCs) of CRF compared to non-CRF aortic sections. Eight genes were implicated in the regulation of the cytoskeleton (including capping protein muscle Z-line 1 alpha and moesin) and cell migration, and five genes were implicated in extracellular matrix function and apoptosis. A trend towards an upregulation of candidate genes involved in arterial calcifications was observed in CRF patients, but did not reach statistical significance. Carotid-femoral pulse wave velocity was not correlated with gene expression level. CONCLUSION: In conclusion, these results show that patients at an early stage of CRF have a specific gene expression profile of aortic tissue and suggest that genes implicated in collagen fibrillogenesis, and VSMCs migration and proliferation, particularly LUM and ODC1, may play a role.

Noninvasive investigation of autonomic activity after carotid stenting or carotid endarterectomy.

OBJECTIVE: Carotid artery stenting (CAS) has been introduced as an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis. Both techniques seem to be associated with postoperative hemodynamic lability. Both may induce baroreceptor dysfunction, possibly leading to transient impairment of cardiovascular autonomic activity and resulting in hemodynamic instability. This instability might contribute to postoperative morbidity. To elucidate these phenomena, we studied the cardiac baroreflex and autonomic cardiovascular control after CAS and CEA. METHOD: In 20 patients scheduled for CAS (n = 10) or CEA (n = 10), intra-arterial pressures and electrocardiograms were recorded during 10 minutes before and 8 and 24 hours after the procedure. Spontaneous cardiac baroreflex sensitivity was assessed using the sequence method and cross-spectral analysis. In addition, cardiovascular autonomic activity was investigated using spectral analysis of heart rate variability and systolic arterial pressure variability. RESULTS: After CAS, we demonstrated an increase of the spontaneous baroreflex sensitivity median (interquartile range) from 5.6 (5.1 to 6.2) ms/mm Hg before the procedure to 8.8 (6.8 to 10.5) ms/mm Hg and 7.7 (3.9 to 8.6) ms/mm Hg (P < .001), 8 and 24 hours after the procedure. This was consistent with the increase of the high frequency component of heart rate variability reflecting cardiac parasympathetic activity and a decrease of the low frequency of systolic arterial pressure variability reflecting sympathetic vascular activity. The postoperative period was also associated with decreased systolic arterial pressure from 173 (162 to 190) mm Hg at baseline to 122 (109 to 143) mm Hg and 136 (121 to 143) mm Hg at 8 and 24 hours after CAS (P < .001). No changes in baroreflex sensitivity or in autonomic activity were observed after CEA. CONCLUSIONS: These preliminary data suggest that CAS is associated with parasympathetic predominance postoperatively and may probably explain the lower systolic arterial pressure observed after CAS.