Coronary Arteriosclerosis, Coronary Artery Disease, DNA Damage, DNA Repair Abnormality
Conditions
Brief summary
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.
Interventions
None listed
Sponsors
University Hospital Southampton NHS Foundation Trust
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required. | This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay. |
| 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. | Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required. | — |
Countries
United Kingdom
Contacts
Primary ContactThomas R Gilpin, MBBCh
Backup ContactZoe Nicholas, BSc
Outcome results
None listed