CVD 1 Flashcards
Major forms of CVD
HTN
Atherosclerosis
Coronary heart disease (CHD)
Peripheral vascular disease (cerebrovascular disease/stroke and deep vein thrombosis)
Congestive heart failure (CHF)
Atherosclerosis definition, associated conditions and potential primary causes
Definition: thickening of blood vessel walls due to presence of atherosclerotic plaque (accumulation of small particle LDL-C)
Associated: MI, CVA/stroke, PVD, CHD, CHF with severe CHD/MI
Causes: high BP, tobacco chemicals, oxidized LDL, glycated proteins, AngII –> low NO
Pathophysiology of atherosclerosis (8)
1) injury to endothelial lining of artery + lipid infiltration ( produces oxidized LDL in intima)
2) Cholesterol accumulates to prevent further rupture
3) Monocytes circulate and respond to injury
4) Monocytes slip under endothelial cells to engulf LDL cholesterol –> foam cells –> form fatty streaks
5) Fatty streaks accumulate lipids, smooth muscle, connective tissue and cellular debris
6) adherence of platelets and release of platelet-derived growth factor
7) cell proliferation (other growth factors) –> atheroma (advanced lesion)
8) Vessels can grow and become vulnerable to rupture or thrombosis
Risk factors for atherosclerosis
Not reversible: age, sex (male), genetics/familial history of premature CVD, <55 male 1° relative or <65 female 1° relative
Reversible: HTN, abdominal obesity, atherogenic diet, smoking, low PA, hyperlipidemia LDL-C, low HDL (<1 mmol/L men, <1.3 mmol/L women)
Role of Apo proteins
Apo proteins are made in enterocytes and hepatocytes and dictate interaction with target tissues
Chylomicrons makeup and role
Apo protein
Deposit triglycerides into non-liver tissue with lipoprotein lipase and fats in blood vessels
Trade TG w/ HDL
20% become chylomicron remnants (smaller chylomicrons) –> liver for more metabolism
Primarily triglycerides - lowest density
Present only in fed state
ApoB-48, ApoE, ApoCII/III (remnants lose C), ApoA-I/IV
VLDL makeup and role
Apo protein
Endogenous lipid transport following a meal from liver and interacts with HDL (receives CE) and then gives phospholipids to HDL, and FA to tissues as it circulates back to liver
May become VLDL remnant
Higher TAG content + phospholipids on surface (lower density than LDL)
Present only in fed state
ApoB-100, ApoE, ApoC (remnants/IDL lose C)
Fates of VLDL remnants
Uptake by hepatic LDL receptors
Hydrolysis by hepatic TAG lipase forming LDL from remnants
LDL makeup and role
Apo protein
Filled with primarily CE, higher apo proteins and phospholipids (more dense and smaller than VLDL)
Transport of CE to tissues
Present in fasted state
1 apoB-100 only
HDL makeup and role
Apo proteins
Enzymes involved reverse cholesterol transport
Primarily apoprotein and phospholipids, some CE (similar to VLDL)
Collects CE from tissues - competes with LDL
ApoA-I, ApoA-II, apoC, and ApoE (allows for competition with VLDL)
Enzymes involved in reverse cholesterol transport:
Lecithin cholesterol acyl transferase (LCAT): acquisition of unesterified cholesterol and esterification
Cholesterol ester transfer protein (CETP): exchange of TAGs to HDL and CE to VLDL
HTGL: hepatic triglyceride lipase to transfer TAGs to liver
3 pathways by which reverse cholesterol transport occurs
Uptake of CE to HDL and esterification by LCAT
1) direct uptake of HDL by liver
2) transfer of CE to VLDL (CETP) –> uptake of VLDL by liver
3) transfer of CE to VLDL (CETP) –> VLDL remnant becomes LDL –> LDL uptake by liver
Overview of cholesterol transport
Intestines (Fed) –> Chylomicrons –> lipoprotein lipase collects TAGS in tissues –> chylomicron remnant –> liver receptors
Liver –> VLDL –> lipoprotein lipase collects fatty acids and phospholipids –> IDL (can go to liver receptor) –> LDL –> liver receptors OR extra-hepatic tissues receptors
HDL collects cholesterol from extra-hepatic tissues, esterifies into CE and delivers to LDL and VLDL and liver
Normal total cholesterol:
Normal HDL: men and women and protective levels
Optimal LDL
Normal triglyceride levels
Normal total cholesterol: <5.2 mmol/L
Normal HDL: Men: >1.0 mmol/L, Women: > 1.3 mmol/L (less is a major risk factor for heart disease)
Protective HDL: >1.5 mmol/L
Optimal LDL: <2.6 mmol/L
Normal triglyceride levels: <1.7 mmol/L
LDL-C equations
mmol/L:
LDL-C = total cholesterol - (HDL-C + TG/2.2)
mg/dL:
LDL-C = total cholesterol - (HDL-C + TG/5)
Apoproteins as indicators of risk of CVD
Types in terms of atherogenicity
Primary determinants of metabolic fate of lipoproteins and changes in lipoprotein composition and concentration in plasma
–> may be better predicts of CVD than lipids and may correlate w/ disease severity
–> can be used to diagnose lipoprotein disorders which put people at higher CVD risk
ApoB: atherogenic
ApoA: non-atherogenic
Apoprotein functions (4)
1) synthesis/secretion of specific lipoproteins (B-100 and VLDL)
2) stabilizes lipoprotein coat
3) activates enzymes (ex. apoC-II activates LPL)
4) Interacts with cell surface receptors (B-11 and LDL receptors)
