Dataset Information

Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome.

ABSTRACT:

Background

The NF-E2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients with chronic coronary syndromes (CCS).

Methods

HO-1 was measured in 526 patients (60 ± 9 years, 318 males) with CCS. Coronary computed tomography angiography (CTA) and stress imaging were used to assess the disease phenotype (coronary atherosclerosis and myocardial ischemia) in a subgroup of 347 patients.

Results

In the overall population, HO-1 median value (25-75 percentile) was 5.195 (1.75-8.25) ng/mL. Patients with higher HO-1 were more frequently male, had a higher BMI and lower LVEF%, but otherwise similar risk factors than the other patients. Their bio-humoral profile was characterized by higher markers of endothelial/myocardial dysfunction, but lower levels of cholesterol lipoproteins. Coronary artery disease was characterized by more diffuse atherosclerosis, with mainly non-obstructive and calcified plaques, and a higher prevalence of functional ischemia.

Conclusion

In patients with CCS, higher plasma HO-1 levels are associated with lower cholesterol and a more diffuse but mainly non-obstructive coronary atherosclerosis, confirming a potential role for the Nrf2/HO-1 pathway as a protective feedback.

SUBMITTER: Caselli C

PROVIDER: S-EPMC8698632 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease (CVD), however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). This study aimed to investigate the expression pattern of exosomal circRNAs in the plasma of CCS patients, and to screen exo-circRNAs that can act as biomarkers for the diagnosis of CCS. Methods: High-throughput sequencing technology was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) (sequencing cohort) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real time polymerase chain reaction (RT-PCR) in a small-sample cohort (derivation cohort) and a large-sample cohort (validation cohort). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exo-circRNAs for CCS patients. Results: By high-throughput sequencing of circRNAs in 15 CCS patients and 15 NCCP patients, 276 circRNAs differentially expressed in plasma exosomes of CCS patients were screened by using |log2(Fold change) |>1 and q-value<0.001, and 103 were up-regulated and 173 were down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels and significantly increased in plasma exosomes of CCS patients were selected for validation. Twice RT-PCR validation demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS (P<0.001). Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve (AUC) values of 0.761 (P<0.001, 95%CI=0.669, 0.852) and 0.623 (P=0.015, 95%CI=0.522, 0.724) for CCS, respectively by ROC curve analysis. Moreover, AUC of hsa_circ_0075269 combined with hsa_circ_0000284 for diagnosing CCS was 0.741 (P<0.001, 95%CI=0.667, 0.850). Conclusion: The expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS diagnosis.