Gene expression analysis identify genes associated with arterial stiffness and carotid diameter in the twins UK cohort

M. Cecelja, B. Jiang, K. McNeill, T. Spector, P. Chowienczyk
2014 Artery Research  
0.16AE1.9 vs -0.12AE2.2 m/s; PZ0.4), or any other haemodynamic variable relative to control at six or 12 months (all P > 0.05). Conclusions: Despite many observational studies to suggest that vitamin D supplementation could be a useful therapy for improving aortic stiffness and associated haemodynamic indices, 12-months intervention yielded no improvement in older people with vitamin D deficiency. These results do not support use of vitamin D supplementation to improve cardiovascular health in
more » ... vascular health in this patient population. 3.5 Beta-blockers are effective in reducing peripheral blood pressure (pBP), but less effective than other drugs in reducing central blood pressure (cBP). It is controversial whether vasodilating (VB) beta-blockers may be more effective in reducing cBP compared to non-vasodilating (NVB) beta-blockers. Methods: a meta-analysis was conducted by selecting randomized trials exploring the effect of beta-blockers on cBP. Twenty-two studies were selected. Comparisons were made between 33 trial arms (NVBZ22,VBZ11). In a random-effect meta-regression model, the following covariates were introduced: treatment (0Zbaseline, 1Ztreatment), drug class (VB vs NVB), interaction term: (treatment x drug class), mean age, study duration, study design, treatment-induced heart rate changes. Results: 1225 subjects (NVBZ908, VBZ317) were included in the analysis. Mean pSBP was 147 mmHg for NVB and 148 mmHg for VB at baseline, and 133 mmHg for NVB and 134 mmHg for VB after treatment. The difference between pSBP and cSBP at baseline (pSBP -cSBP) was 12.9 mmHg for NVB and 13.4 mmHg for VB. Treatment with either VB or NVB determined a reduction of the above difference to 8.6 mmHg for NVB and 11.3 mmHg for VB (both p<0.01). In the final model, the effect of drug class on the difference between pSBP and cSBP (after treatment -baseline) was not significantly smaller for VB (-2.1 mmHg) than for NVB (-4.3 mmHg; pZ 0.09). Conclusions: VB have a marginally, although not significantly, less unfavourable effects on cSBP than NVB. The blood pressure-lowering effect of betablockers is more pronounced for pSBP than for cSBP. GENE EXPRESSION ANALYSIS IDENTIFY GENES ASSOCIATED WITH ARTERIAL STIFFNESS AND CAROTID DIAMETER IN THE TWINS UK COHORT Background: Previous studies have identified several genetic variants associated with arterial stiffness. The aim of this study was to investigate whether expression profiles of these genes associate with measures of aortic stiffness and diameter. Method and Results: In a cross-sectional study of 2092 women aged 21-84 years from the TwinsUK cohort, measures of aortic stiffness (carotid-femoral pulse wave velocity [PWV], carotid distensibility), carotid diameter and heritability were made. In a subsample (nZ470), gene expression levels of 62 genes previously associated with PWV were measured in leukocytes with Affymetrix microarrays. PWV and carotid diameter increased by 75% and 18%, respectively, from the second to seventh decade. Carotid distensibility decreased by 73%. Pleiotropic genetic effects accounted for 53% of the phenotypic correlation between carotid distensibility and diameter. Leukocyte-derived transcript ENPP1 significantly correlated with PWV. In 121 women that had repeat vascular measures over a follow-up period of 4.3AE1.4 years, leukocyte-derived ENPP1 expression and COL4A1 strongly related to PWV progression in multivariable regression (betaZ0.19, p<0.01 and betaZ0.32, p<0.0001; respectively). For carotid distensibility, leukocyte-derived transcript for angiotensin converting enzyme (ACE) most strongly associated with a reduction in carotid distensibility (betaZ-0.20, p<0.001). Expression levels of ACE gene also associated with progression in carotid diameter (betaZ0.21, p<0.05). Conclusion: This study demonstrates that expression levels of ENPP1, which associated with arterial calcification, and COL4A1, associated with collagen
doi:10.1016/j.artres.2014.09.068 fatcat:eftjimxk4zhslj6grc7n7r32mm