DNA Repair in Patients With Stable Angina.

University Hospital Southampton NHS Foundation Trust172 enrolled

Overview

Markers of DNA damage and repair are present in both atherosclerotic plaques and peripheral blood mononuclear cells of patients with coronary artery disease. A positive correlation has been observed between the level of DNA damage and the severity of atherosclerotic lesions, as well as atherogenic risk factors such as smoking, hypertension and hyperlipidaemia. A number of in-vitro studies have implicated defective DNA repair in the development and progression of atherosclerotic lesions. In mouse models of atherosclerosis, the DNA repair signalling cascade has been shown to be amenable to pharmacological intervention and overexpression of specific repair proteins attenuate the development of atherosclerotic plaques. However, data regarding the role of DNA repair in the pathogenesis of atherosclerosis in humans are lacking. We have preliminary data indicating reduced DNA repair activity in patients with stable angina. This study will determine the molecular basis and the biological consequences of this observation.

Study Type

OBSERVATIONAL

Enrollment

172

Conditions

Coronary Artery Disease Coronary Arteriosclerosis DNA Damage DNA Repair Abnormality

Eligibility

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years * Ability to provide written informed consent Exclusion Criteria: * Age ≥ 80 years * Inability to provide written informed consent * Presentation with an acute coronary syndrome * Severe valvular heart disease * Hypertrophic cardiomyopathy * Left ventricular ejection fraction ≤ 35% * Prior coronary revascularisation (surgical or percutaneous) * Diabetes Mellitus * Clinical evidence of peripheral vascular disease * Prior history of cerebrovascular disease * Malignancy * Active inflammatory disorders (e.g. rheumatoid arthritis/connective tissue disorder) * Renal impairment eGFR \<60ml/min/1.73m2 * Anaemia (Hb \<100g/dL)

Outcomes

Primary Outcomes

Association between monocytes exhibiting reduced base excision repair and/or double strand break repair activity in patients with stable angina as compared to patients without coronary artery disease.

This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay.

Time frame: Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required.

Reduced DNA repair activity is associated with impaired response to oxidative stress in human monocytes in patients with stable angina in comparison to an age and gender matched control.