Serum lipids and CVD

FNN200

Elevated levels for cholesterol and TGS (CVD risk factor)

• total cholesterol >5.2mmol/L

• Serum Triglycerides >1.7mmol/L

Cholesterol

• mainly synthesized in the liver

• not used for energy

• mainly eliminated in liver

Cholesterol production enzyme

• HMG-CoA reductase

Control of cholesterol producton

• negative feedback

• cholesterol will allosterically reculate the enzyme HMG-CoA reductase

Reducing cholesterol

• dietart changes (fats and sugars) 

• Increased exercise 

  • can increaase HDL and may lower LDL

• Weight reduction (if necesary)

• Metabolism drugs 

  • Phyrosterols (reduce uptake)

  • statin drugs (inhibit synthesis → impact HMG-CoA reductase)

  • Reduce absorption (Ezetimibe → inhibition of absorption)

  • Inhibit bile reuptake 

Lipid and protein composition of lipoprotein classes

• Exogenous transporter

  • chylomicron (least dense with the most triglycerides)

• Endogenous transporters 

  • VLDL

    • least dense

    • most triglycerides

  • IDL

  • LDL

    • Contains the most cholesterol

  • HDL

    • most dense

    • most protein

Apoproteins

• Attach to the lipoproteins and mark them for transportation and are able to be markers of health based on which they are attached to 

ApoA1 

• Chylomicrons and HDL 

• can be a marker of health on HDL 

Lipoprotein lipase

• function in removing triglycerides from the chylomicron before they go on the to the liver

• results in glycerol in blood stream

• Makes the chylomicron remnant 

ApoB-100

• On VLDL, IDL and LDL

• Signal of bad cholesterol

• Endogenous cholesterol transport

• Starts on nascent VLDL, then mature VLDL

  • then Lipoprotein lipase will remove some triglycerides and make blood glycerol and form IDL

  • glycerol is releassed by hydrolysis

• IDL is the shrunk version of VLDL and becomes LDL

LDL Receptors

• LDL Receptors take up LDL from the blood 

• they attach to the ApoB-100 apoprotein and that is what the receptor is actually using 

  • Takes in the receptor LDL complex, degrades LDL into cholesterol 

    • membrane synthesis, steroid hormones, bile acids 

  • receptor is recycled 

Bile acids and LDL receptors

• Viscous fibers, take up bile

• this results in increased LDL receptors to take in LDL to create more bile acids, 

  • clears some of the bad cholesterol from the blood 

HDL metabolism: reverse cholesterol transport

• HDL is formed in intestine and liver 

  • has ApoA1 on it 

• Nascent HDL is discoidal then LCAT converts it into spherical particles with cholesterol core 

  • esterifies the free cholesterol that is stored in core of HDL 

• ABCA1in the cells and gives it to HDL to bring to liver to be removed from body 

• SR-B1 is the receptor that takes in cholesterol esters from HDL 

LCAT

• Lecithin-cholesterol Acyl-transferase 

• responsible for making mature HDL particles 

• Esterifies the free cholesterol in the core

  • enables a more tightly packed HDL particle that can more efficiently clear the cell of Cholesterol 

• would be a marker of reduced CVD risk 

  • higher HDL

ABCA1

• found on the surface of cells not on the actual lipoproteins 

  • responsible for transporting of cholesterol and phospholipids to HDL molecules

  • Prevents cholesterol from building up in the cells

  • cholesterol is transfered from the ABCA1 on to ApoA1 proteins

• High ABCA1 is a marker of good cardiovascular health as it helps to promote reverse cholesterol transport

Lipoprotein A

• modified form of LDL

  • independent risk factor for heart disease

  • 70-90% influenced by genetics

  • not influenced by diet

  • highest in black/african individuals and south asians

  • Levels are independent of the levels of LDL

Lipid screening in ontario

• types of cholesterol

  • LDL, HDL, Total, Total/HDL

• Triglycerides

• Types of Lipoproteins 

  • ApoB is a stronger indivator of atherosclerotic CVD than LDL-C 

    • it is on every VLDL, IDL and LDL

    • May be more acurate preditcor of heart disease risk in some patients (with diabetes or high Triglycerides)

  • ApoA1 ratio is not covered by OHIP

  • Lipoprotein(a) is not covered by OHIP but is reccomended if oyu have family history of heart disease

Development of Atherosclerosis

• Initiating factor 

  • injury to the wall of the artery 

• Oxidized LDL-cholesterol goes into the artery → gets taken up by macrophages whcih created cholesterol foam cells 

  • these wil then form fatty streaks whcih become plaques 

• the lipid core gets a fibrous cap which can burst releaseing the lipid core and also creating blood clots 

  • blocks oxgen supply to heart and brain 

Increases in heart risk blood lipids

• High LDL

• Low HDL 

• High total cholesterol 

• High triglycerides 

• high non HDL cholesterol 

• high total/HDL cholesterol ratio 

Increased risk factors for CVD disease

• diabetes

• high blood pressure

• overweight body mass 

Lifestyle icnreases in CVD risk

• smoking

• sedentary lifestyle 

• high saturated fat diet, low fiber diet, low unsat fats low veg

N-3 protection of dietary fat and blood lipids - anti-inflammatory mechanisms

• Circulating inflammatory markers

  • decreased inflammatory cytokines

• Eicosanoid synthesis

  • decreasing production of N-6 and increase N-3

  • specialized pro-resolving mediators (resolvins and protectins)

• Gene expression

  • epigenetic mechanisms

  • nuclear receptors and transcription factors

    • natural ligands

• Incorporation into cell membranes

  • lipid rafts → forming large raft domains

  • impared cell signalling and supression of cell activation

  • membrane channels and proteins

    • modulation of ion channels 

• Physiological effects 

  • triglycerides → improved blood lipids

  • Heart rate → decreased heart rate 

  • Vascular → decreased blood pressure and systemic vascular resistance 

Fat DRIs

• 20-35% energy

• AI for linoleic (n-6) should be 5-10% of energy 

• AI for alinolenic acid (n-3) 0.6-1.2% of energy 

  • some say ratio for these are actually to high

• Saturated, trans, and cholesterol low as possible 

• replace sat with MUFA and PUFA where possible