Whole Blood Gene Expression Testing for Coronary Artery Disease in Nondiabetic Patients: Major Adverse Cardiovascular Events and Interventions in the PREDICT Trial

Owing to the dynamic nature of the transcriptome, gene expression profiling is a promising tool for discovery of disease-related genes and biological pathways. In the present study, we examined gene expression in whole blood of 12 patients with CAD (coronary artery disease) and 12 healthy control subjects. Furthermore, ten patients with CAD underwent whole-blood gene expression analysis before and after the completion of a cardiac rehabilitation programme following surgical coronary revascularization. mRNA and miRNA (microRNA) were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in patients with CAD compared with healthy controls (175 up- and 190 down-regulated in CAD), and 645 in CAD rehabilitation patients (196 up- and 449 down-regulated post-rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups. Analysis of miRNA expression revealed a number of differentially expressed miRNAs, including hsa-miR-140-3p (control compared with CAD, P=0.017), hsa-miR-182 (control compared with CAD, P=0.093), hsa-miR-92a and hsa-miR-92b (post- compared with pre-exercise, P<0.01). Global analysis of predicted miRNA targets found significantly reduced expression of genes with target regions compared with those without: hsa-miR-140-3p (P=0.002), hsa-miR-182 (P=0.001), hsa-miR-92a and hsa-miR-92b (P=2.2×10−16). In conclusion, using whole blood as a ‘surrogate tissue’ in patients with CAD, we have identified differentially expressed miRNAs, differentially regulated genes and modulated pathways which warrant further investigation in the setting of cardiovascular function. This approach may represent a novel non-invasive strategy to unravel potentially modifiable pathways and possible therapeutic targets in cardiovascular disease.

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The Effects of Metabolic Syndrome Versus Infectious Burden on Inflammation, Severity of Coronary Atherosclerosis, and Major Adverse Cardiovascular Events

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-2428 ◽

2007 ◽

Vol 92 (7) ◽

pp. 2532-2537 ◽

Cited By ~ 13

Author(s):

Dao-Fu Dai ◽

Jou-Wei Lin ◽

Jia-Horng Kao ◽

Chih-Neng Hsu ◽

Fu-Tien Chiang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Metabolic Syndrome ◽

Coronary Artery ◽

Cardiovascular Events ◽

Coronary Atherosclerosis ◽

Major Adverse Cardiovascular Events ◽

Gensini Score ◽

Clinical Predictors ◽

Artery Disease ◽

Infectious Burden

Abstract Background: The clinical predictors of inflammation in atherosclerosis remain controversial. The objective of this study was to compare the associations of metabolic factors vs. infectious burden (IB) with inflammation, the severity of coronary atherosclerosis, and major adverse cardiovascular events (MACEs). Design, Setting, and Patients: Coronary angiography with Gensini score was applied to assess the severity of coronary atherosclerosis in 568 patients with coronary artery disease. Metabolic syndrome (MS) score (0–5) was defined according to the modified criteria of National Cholesterol Education Program Adult Treatment Panel III. IB score (0–7) was defined as the number of seropositivities to several agents. Results: IB score was not associated with plasma C-reactive protein (CRP) concentration, Gensini score, or the risk of MACE. In contrast, MS score significantly correlated with both plasma CRP concentration and Gensini score (P < 0.001 for both). MS score and plasma CRP concentration were also significantly associated with the risk of MACE (hazard ratios 1.51, P < 0.001; and 1.90, P = 0.002, respectively). Conclusion: Compared with IB, metabolic abnormalities have a more prominent association with the degree of inflammation, the severity of coronary atherosclerosis, and the risk of MACE in patients with coronary artery disease.

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Distinct Characteristics of VEGF‐D and VEGF‐C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease

Journal of the American Heart Association ◽

10.1161/jaha.119.015761 ◽

2020 ◽

Vol 9 (9) ◽

Cited By ~ 2

Author(s):

Hiromichi Wada ◽

Masahiro Suzuki ◽

Morihiro Matsuda ◽

Yoichi Ajiro ◽

Tsuyoshi Shinozaki ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Angiography ◽

Cardiovascular Events ◽

Troponin I ◽

Cardiovascular Death ◽

Major Adverse Cardiovascular Events ◽

All Cause Mortality ◽

Artery Disease ◽

Cardiovascular Biomarkers

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

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