Dyslipidemia

Darmono SS

Sources of lipid
‡ ‡ ‡ ‡ ‡ ‡ Saturated and unsaturated (mono & poly) Fat, animal fat Oil, coconut oil, corn oil, olive oil, Vegetable oil (n-6) Trans lipid Fish oil (n-3)

Lipid
‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ Energy sources Organ protected (burse) Cellular structural development Essential fatty acid sources Vitamin solubility Prostaglandin precursor Steroid hormone synthesis palatability

Fatty Acid
‡ All saturated fats are equally to cholesterolemia ? ‡ Laurie, myristic risk of diseases ‡ Unsaturated vegetable oils : frequently hydrogenated to produce more solid, stable fats process, an assortment of cis & trans isomers tend to raise LDL & lower HDL. ‡ Characteristic of FA : branched chain, conjugated, short chain, long, brominated ‡ Trans FA isomer are a side product of catalytic hydrogenation of vegetable oils and biohydrogenation in the ruminants of animals

Lipid as disease risk factors
‡ Related to cerebro vascular disease (CVD)
± Athero, arterio schlerosis ± Hypertension ± Stroke ± Ischemic heart diseases ± Hypaestesia, paraestesia

FA as diseases risk factor ?
‡ Cholesterol is a critical fat that is a structural component of cell membrane and plasma lipoproteins, and is important in the synthesis of steroid hormones, glucocorticoids, and bile acids. ‡ Hydrogenated veg oil (shortening) ~saturated fat ? Isomer cis (liquid) & trans ‡ Ruminant fats (meat,diary product) ‡ Trans FA are metabolically different from CIS and saturated FA ‡ Trans FA may diseases affect ?

PUFA Function
‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ Membrane cell Mitochondria Nuclei Fluidicity Aggregation Diffusional movement Affinity of receptor Membrant permeability Transport property

PUFA function
‡ ‡ ‡ ‡ ‡ ‡ ‡ Abnormally swelling ? Decreases capillary resistance Fragility of erythrocyte Integrity maintenance Epidermal water barrier Immune response T cell dependent antigens.

Lipoprotein
‡ Spherical particles, made up of hundreds lipid and protein molecules. ‡ Much smaller than red blood cell, visible only with electro microscope. ‡ Triglyceride rich lipoprotein, high protein plasma to be turbid & milky ‡ Insoluble in aqueous environments (hydrophobic)

Lipoprotein, Apoproteins
‡ The surface proteins of the lipoproteins are called apoproteins or apolipoproteins ‡ Groupingthe major lipoprotein clases (9) apoproteins. ‡ Essential for assembly & secretion of chylomicrons is apo B 48 ‡ Constitutes of 48 % of the amino terminal end of apo B 100 major apoproteins of VLDL, IDL, LDL ame gene and messenger RNA as apo B 100 ‡ 8 hours remaining lipoprotein in blood stream, after last meal

Lipoprotein
‡ Cholesteryl linoleate is formed in plasma by the action of the enzyme lecithin chholesterol actyltransferase (LCAT) ‡ Cholesteryl oleate product of the intracellular enzyme acyl coenzyme A acyltransferase (ACAT)

Lipid, diseases pathogenesis
‡ Influenced by hormonal aspect (Leptin) expressed in adiposa tissues producing lipoprotein lipase ‡ Involving in hydrolyzing the triglycerides and lipoprotein ‡ Adopsin (energy sources) complement ‡ Producing : cytokinine, tumor necrosis factor alpha, angiotensin

Atherosclerotic pathogenesis
Dyslipidemia ‡ Endothelial damage ‡ Induction of endothelial gene expression by mildly oxidized lipoproteins ‡ Increased suspectibility to oxidation of small dense lipoproteins ‡ Lipid accumulation
‡ Intracellular accumulation of modified lipoproteins ‡ Extracellular lipid binding to matrix

‡ Procoangulant effects
‡ Induction of tissue factor and PAI-1 by oxidizied LDL peningkatan activity if factor VII and X and PAI-1 in hypertriglyceridemia

‡ Reduced cholesterol efflux from cells in presence of low HDL

Atherosclerotic pathogenesis
Oxiative factors ‡ Endothelial damage
Endothelial permeability intimal plasma protein retention

‡ Procoagulant effects
platelet aggregation fibrinogen levels thromboxane A2 production

‡ Lipoprotein
HDL LDL, VLDL Lipoprotein oxidation

Atherosclerosis pathogenesis
Vascular vasoconstrictino ‡ Endothelium
monocyte adherence, infiltration

‡ Immune dysfunction
Macrophage proliferation lymphocyte -receptor responsiveness

‡ Angiotensin II-mediated effects
SMC matrix protein synthesis (e.g, -actin) SMC cytokine synthesis (e.g, PDGF A-chin, TGF ) Macrophage cytokine expression (e.g, HB-EGF)

Athero Schlerosis patogenesis processes
‡ ‡ ‡ ‡ ‡ ‡ Artherio intima alteration Lipid deposit Complex CHO, blood composite Fibrous mass development Calcification Tunica media artherio impairment

Dyslipidemia
‡ Syndrom x : consensus before NCEP AT, the deadly quartet metabolic. ‡ WHO, 2005 :
± Obesity ± Hyperuricemia ± Hypertension ± CVD (IHD)

Dyslipidemia
‡ National cholesterol education program expert panel on detection, evaluation and treatment of high blood cholesterol in adults treatment panel III (NCEP ATP III) on metabolic syndrome (2005), which insulin resistance.

Criteria
‡ Risk of car vascular disease (lipid and non lipid) ‡ Central obesity > 90 cm > 80 cm ‡ Atherogenic dyslipidemia (triglyceride & LDL) ‡ Hypertension ‡ Abnormal plasma glucose

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