- Week 21: Atherosclerosis and CVD - Lipids: non-polar, small amounts are bound to blood proteins and transported as free fatty acids, majority as particles (not molecules), the apoldprotein def i nes lipoprotein - HDL, LDL, IDL, VLDL, chloromicron - LDL is 50% cholesterol - Core of lipoproteins is composed of cholesterol and cholesterol esters. - Cholesterol: component of cell membranes, myelin around nerve cells, bile to allow digestion of dietary lipids, vitD and range of steroid hormones -CholesterolsynthesisisregulatedbyHMG-CoA-reductaseastheratelimitingstep - Increased LDL is a risk factor for atherosclerosis, stroke and CV disease, decreased HDL also a risk factor as HDL clears cholesterol therefore reduced LDL conc. - Balance is key - Innate immunity: fast and blunt, generally through macrophage mediated phagocytosis, involved pattern recognition receptors like Toll-like receptors (TLR), triggersinflammatorycascadeofpro-inflammatorycytokinesincludingMMPs, identif i es 100s of targets only - Adaptive immunity: slow and precise, weeks/months to mount a full change, potential to recognise millions of targets -Pro-inflammatoryenvironmentcanprimethebodyandleadtoenhanced atherosclerosis, - Intima-media thickness: early response to increased bp - Early events: high sheer stress promotes NOS expression leading to increased NO - Low sheer stress decreases NOS expression leading to low levels of NO - WBC leukocyte "rolling" : passive diff usion trying to eat lipid, allowing binding and Acculmalate as fatty streaks - LDL - mo-LDL (modif i ed LDL) -ox-LDL
- Fatty streak formation (f i rst visible sign of atherosclerosis) - Fibrous plaque formation - Ultrasound detection, MRI, - Advanced lesions and thrombosis: single biggest cause of stroke and acute coronary events is plaque rupture, not the degree of stenosis - Arteries can be "stented" to keep them open, stable plaques have the potential to expand and block a vessel or rupture, produce emboli and cause MI or stroke - Genetic predisposition: Familial hypercholesterolemia - Biomarkers Coronary artery disease (CAD) (IHD) (CHD) - disrupted blood f I ow to heart arteries Angina - pain in the chest with exertion (stable) or irregularly (unstable) Myocardial infarction (heart attack) - loss of blood f I ow to part of heart, damaging muscle Arrhythmia - irregular heart beat for a variety number of reasons Valvular heart disease - failure to close fully, heard with stethascope Carditis - inf I ammation of the heart or valves (bacterial endocarditis) Peripheral vascular disease (PVD) - poor arterial f I ow distal circulation Venous thrombosis - emboli and clotting in veins due to poor f I ow Thickeningofleftventriclewallanddilatedchamber,leadingtolessefficientbloodflow Few outward signs, possibly shortness of breath or leg swelling Can be a source of sudden cardiac death (SADS) - aortic aneurysm: A swelling, def i ned as 1.5x or larger normal size, of the descending aorta. Few if any symptoms until late stage disease, diagnosis usually 65+. Also called abdominal aortic aneurysm (AAA), can weaken vessel wall and rupture, causing massive blood loss and usually death unless immediate surgery (10% survival) - Stroke - Focal neurological def i cit usually of sudden onset due to vascular cause - Strokes 20% haemorrhagic 80% ischaemic