پروتين دهني مرتفع الكثافة

الپروتين الدهني مرتفع الكثافة High-density lipoprotein (HDL) هو أحد خمس مجموعات أساسية من الپروتين الدهنية المرتبة حسب الحجم، من الأكبر إلى الأصغر، پروتين دهني وضعي الكثافة، پروتين دهني متوسط الكثافة، الپروتين الدهني منخفض الكثافة، ثم پروتين دهني مرتفع الكثافة، والتي يمكنها نقل الدهون مثل الكوليسترول وثلاثي الگليسريدات مع المحلول المائي لتيار الدم. في الأفراد الأصحاء، يحمل حوالي 13% من كوليسترول الدم پروتينات دهنية مرتفعة الكثافة.[1] ويمكن تعيين نوع الكولسترول استنادًا إلى نوع الپروتين الدهني الذي يحمله. ويوجد البروتين الدهني المنخفض الكثافة في جدران شرايين القلب. ويعتقد بعض العلماء أن البروتينات الدهنية العالية الكثافة تساعد على إزالة الكولسترول من الأنسجة. ويوجد لدى الأشخاص بصفة عامة كولسترول البروتين الدهني المنخفض الكثافة أكثر من كولسترول البروتين الدهني العالي الكثافة.[2]

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

التركيب والوظيفة

HDL is the smallest of the lipoprotein particles. They are the densest because they contain the highest proportion of protein and cholesterol. Their most abundant apolipoproteins are apo A-I and apo A-II.[3] The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles. They are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1). A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually making the newly synthesized HDL spherical. They increase in size as they circulate through the bloodstream and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, for example by the interaction with the ABCG1 transporter and the phospholipid transport protein (PLTP).

HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary, and testes by direct and indirect pathways. HDL is removed by HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans, probably the most relevant pathway is the indirect one, which is mediated by cholesteryl ester transfer protein (CETP). This protein exchanges triglycerides of VLDL against cholesteryl esters of HDL. As the result, VLDLs are processed to LDL, which are removed from the circulation by the LDL receptor pathway. The triglycerides are not stable in HDL, but degraded by hepatic lipase so that finally small HDL particles are left, which restart the uptake of cholesterol from cells.

The cholesterol delivered to the liver is excreted into the bile and, hence, intestine either directly or indirectly after conversion into bile acids. Delivery of HDL cholesterol to adrenals, ovaries, and testes is important for the synthesis of steroid hormones.

Hdl1.svg

Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid-laden macrophages of atherosclerotic arteries, termed foam cells, to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL toward atherosclerosis.

However, HDL carries many lipid and protein species, several of which have very low concentrations but are biologically very active. For example, HDL and their protein and lipid constituents help to inhibit oxidation, inflammation, activation of the endothelium, coagulation, and platelet aggregation. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known what are the most important.

In the stress response, serum amyloid A, which is one of the acute-phase proteins and an apolipoprotein, is under the stimulation of cytokines (IL-1, IL-6), and cortisol produced in the adrenal cortex and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in the tissues manifests itself as amyloidosis.

It has been postulated that the concentration of large HDL particles more accurately reflects protective action, as opposed to the concentration of total HDL particles.[4] This ratio of large HDL to total HDL particles varies widely and is measured only by more sophisticated lipoprotein assays using either electrophoresis (the original method developed in the 1970s) or newer NMR spectroscopy methods (See also: NMR and spectroscopy), developed in the 1990s.


علم الأوبئة

Men tend to have noticeably lower HDL levels, with smaller size and lower cholesterol content, than women. Men also have an increased incidence of atherosclerotic heart disease. Alcohol consumption tends to raise HDL levels[5], and moderate alcohol consumption is associated with lower cardiovascular and all-cause mortality.

Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction. Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase the risk for atherosclerotic diseases.

Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low[بحاجة لمصدر]. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high[بحاجة لمصدر].

Even people with very low LDL levels are exposed to increased risk if their HDL levels are not high enough.[6]

تقدير جسميات البروتينات المرتفعة في الكوليسترول

Reference ranges for blood tests, comparing HDL cholesterol (in orange at right) to other blood constituents.

Many laboratories used a two-step method: Chemical precipitation of lipoproteins containing apoprotein B, then calculating HDL associated cholesterol as the cholesterol remaining in the supernate,[7] and there are also direct methods. Both methods have long been promoted on the basis of lowest cost, though neither of these measurements directly, or reliably, reflect HDL particle functionality to remove cholesterol from atherosclerotic plaque and can therefor be misleading, especially on an individual patient by patient basis[8] Labs use the routine dextran sulfate-Mg2+ precipitation method with ultracentrifugation/dextran sulfate-Mg2+ precipitation as reference method.[9] HPLC can be used.[10]

Subfractions (HDL-2C, HDL-3C) can be measured [11] and have clinical significance.

النطاقات الموصى بها

The American Heart Association, NIH and NCEP provides a set of guidelines for fasting HDL levels and risk for heart disease.[12][13][14]

Level mg/dL Level mmol/L Interpretation
<40 for men, <50 for women <1.03 Low HDL cholesterol, heightened risk for heart disease
40–59 1.03–1.55 Medium HDL level
>60 >1.55 High HDL level, optimal condition considered protective against heart disease

قياس تركيز الپروتين الدهني المرتفع الكثافة

As technology has reduced costs and clinical trial have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations, and size (which indicates function) at lower costs have become increasingly available and regarded as more important for assessing individual risk for progressive arterial disease and improve treatment methods.

قياسات كيميائية

HDL, as discussed above, forms from two large proteins, predominantly apo A-I and apo A-II, positioned, back to back. Charged amino acids on the outer surface attract water, making the particles both water soluble (so as to carry fats within the blood) and able to associate with HDL receptors on in the surface of cells, e.g. the macrophages of which plaque is predominantly composed, at least in the early stages. Cholesterol is carried within and between the two particles. If the particles pick up more cholesterol, then the particles enlarge and a third or fourth apo A protein joins the grouping, termed large HDL. Chemical measurements can be used to estimate HDL concentrations present in a blood sample, though such measurements may not indicate how well the HDL particles are functioning to reverse transport cholesterol from tissues. HDL-cholesterol is measured by first removing LDL particles by aggregation or precipitation with divalent ions (such as Mg++) and then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate.

قياسات كهربائية

Since the HDL particles have a net negative charge and vary by size, electrophoresis measurements have been utilized since the 1960s to both indicate the number of HDL particles and additionally sort them by size, thus presumably function. Larger HDL particles are carrying more cholesterol.

قياسات بالرنين المغناطيسي الذري

The newest methodology for measuring HDL particles, available clinically since the late 1990s [1] uses Nuclear Magnetic Resonance fingerprinting of the particles to measure both concentration and sizes. This methodology has reduced costs relative to ultracentrifugation.

التركيات الكبرى والمثلى للپروتين الدهني المرتفع الكثافة

The HDL particle concentrations are typically categorized by event rate percentiles based on the people participating and being tracked in the MESA [2] trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute.

Total HDL particle Table

MESA Percentile Total HDL particles μmol/L Interpretation
>75% >34.9 Those with highest (Optimal) total HDL particle concentrations & lowest rates of cardiovascular disease events
50–75% 30.5–34.5 Those with moderately high total HDL particle concentrations & moderate rates of cardiovascular disease events
25–50% 26.7–30.5 Those with lower total HDL particle concentrations & Borderline-High rates of cardiovascular disease
0–25% <26.7 Those with lowest total HDL particle concentrations & Highest rates of cardiovascular disease events

Large (protective) HDL particle Table

MESA Percentile Large HDL particles μmol/L Interpretation
>75% >7.3 Those with highest (Optimal) Large HDL particle concentrations & lowest rates of cardiovascular disease events
50–75% 4.8–7.3 Those with moderately high Large HDL particle concentrations & moderate rates of cardiovascular disease events
25–50% 3.1–4.8 Those with lower Large HDL particle concentrations & Borderline-High rates of cardiovascular disease
0–25% <3.1 Those with lowest Large HDL particle concentrations & Highest rates of cardiovascular disease events

The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles, the top quarter (>75%), and the highest concentrations of large HDL particle concentrations. Multiple other measures, including LDL particle concentrations, small LDL particle concentrations, along with VLDL concentrations, estimations of Insulin resistance pattern and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are also routinely provided.


. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

الذاكرة

Fasting serum lipids have been associated with short term verbal memory. In a large sample of middle aged adults, low HDL cholesterol were associated with poor memory and decreasing levels over a five year follow-up period were associated with decline in memory.[15]

طرق لزيادة تركيز الپروتين الدهني المرتفع الكثافة

النظام الغذائي وأسلوب الحياة

Certain changes in lifestyle may have a positive impact on raising HDL levels:[16]

Most saturated fats increase HDL cholesterol to varying degrees but also raise total and LDL cholesterol.[29] A high-fat, adequate-protein, low-carbohydrate ketogenic diet may have similar response to taking niacin as described below (lowered LDL and increased HDL) through beta-hydroxybutyrate coupling the Niacin receptor 1.[30]

الأدوية

While higher HDL levels are correlated with cardiovascular health, no incremental increase in HDL has been proven to improve health. In other words, while high HDL levels might correlate with better cardiovascular health, specifically increasing one's HDL might not increase cardiovascular health.[31] Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and niacin. Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids.[32] Similarly, increased HDL levels from niacin have not been shown to be efficacious in reducing cardiovascular disease in a randomized controlled trial.[31]

Niacin (vitamin B3), increases HDL by selectively inhibiting hepatic Diacylglycerol acyltransferase 2, reducing triglyceride synthesis and VLDL secretion through a receptor HM74[33] otherwise known as Niacin receptor 2 and HM74A / GPR109A,[30] Niacin receptor 1.

Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%,[34] making it the most powerful agent to increase HDL-cholesterol.[35][36] A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events.[37] However, niacin products sold as "no-flush", i.e. not having side-effects such as "niacin flush", do not contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest, immediate-release preparation.[38] Both fibrates and niacin increase artery toxic homocysteine, an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins[بحاجة لمصدر], however multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates. A 2011 niacin study was halted early because patients showed no increase in heart health, but did experience an increase in the risk of stroke.[39]

In contrast, while the use of statins is effective against high levels of LDL cholesterol, it has little or no effect in raising HDL cholesterol.[35]

Magnesium supplements raise HDL-C.[40]

Apo-A1 Milano, the most effective proven HDL agent, is in commercial production by a Canadian company, Sembiosys, but as of 2010 may still be several years away from clinical availability.[بحاجة لمصدر]

انظر أيضا

هوامش

  1. ^ "LDL and HDL Cholesterol: What's Bad and What's Good?". American Heart Association. يوليو 2, 2009. Retrieved أكتوبر 8, 2009.
  2. ^ الكوليسترول، الموسوعة المعرفة الشاملة
  3. ^ Després, Jean-Pierre. "The Atherogenic Triad of New Metabolic Risk Factors: Importance of Waist and Fasting Triglycerides as Screening Tools". Visceral Adipose Tissue and Cardiometabolic Risk: Does It Really Matter? Part 2. Retrieved أكتوبر 8, 2009.[نشر ذاتي سطري?]
  4. ^ PMID 11374859 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  5. ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1732002/pdf/v056p00024.pdf
  6. ^ Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles (2007). "HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events". New England Journal of Medicine. 357 (13): 1301. doi:10.1056/NEJMoa064278. PMID 17898099.
  7. ^ Lin, Maun-Jan; Hoke, Carolyn; Ettinger, Bruce (1998). "Evaluation of Homogeneous High-Density Lipoprotein Cholesterol Assay on a BM/Hitachi 747-200 Analyzer". Clinical Chemistry. 44 (5): 1050. PMID 9590383.
  8. ^ "Lipid Measurement Fact Sheet". University of Michigan Health System. Retrieved أكتوبر 8, 2009.
  9. ^ Bairaktari, E; Elisaf, M; Katsaraki, A; Tsimihodimos, V; Tselepis, AD; Siamopoulos, KC; Tsolas, O (1999). "Homogeneous HDL-cholesterol assay versus ultracentrifugation/dextran sulfate-Mg2+ precipitation and dextran sulfate-Mg2+ precipitation in healthy population and in hemodialysis patients". Clinical Biochemistry. 32 (5): 339. doi:10.1016/S0009-9120(99)00031-4. PMID 10480448.
  10. ^ Okazaki, Mitsuyo; Sasamoto, Keiko; Muramatsu, Toshio; Hosaki, Seijin (1997). "Evaluation of precipitation and direct methods for HDL-cholesterol assay by HPLC". Clinical Chemistry. 43 (10): 1885. PMID 9342008.
  11. ^ Hirano, Tsutomu; Nohtomi, Kyoko; Koba, Shinji; Muroi, Ayako; Ito, Yasuki (2008). "A simple and precise method for measuring HDL-cholesterol subfractions by a single precipitation followed by homogenous HDL-cholesterol assay". The Journal of Lipid Research. 49 (5): 1130. doi:10.1194/jlr.D700027-JLR200. PMID 18223297.
  12. ^ "Cholesterol Levels". American Heart Association. Retrieved نوفمبر 14, 2009.
  13. ^ "What Do My Cholesterol Levels Mean?" (PDF). American Heart Association. سبتمبر 2007. Retrieved نوفمبر 14, 2009.
  14. ^ "Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Executive Summary" (PDF). National Heart, Lung, and Blood Institute (NHLBI). National Institutes of Health. مايو 2001.
  15. ^ Singh-manoux, A; Gimeno, D; Kivimaki, M; Brunner, E; Marmot, MG (2008). "Low HDL cholesterol is a risk factor for deficit and decline in memory in midlife: the Whitehall II study". Arteriosclerosis, thrombosis, and vascular biology. 28 (8): 1556–62. doi:10.1161/ATVBAHA.108.163998. PMC 2581752. PMID 18591462.
  16. ^ Fogoros, Richard N. (سبتمبر 15, 2009). "Raising Your HDL Levels". About.com. Retrieved أكتوبر 8, 2009.
  17. ^ Spate-douglas, T; Keyser, RE (1999). "Exercise intensity: its effect on the high-density lipoprotein profile". Archives of physical medicine and rehabilitation. 80 (6): 691–5. doi:10.1016/S0003-9993(99)90174-0. PMID 10378497.
  18. ^ أ ب ت Hausenloy DJ, Yellon DM (2008). "Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels". Heart. 94 (6): 706–14. doi:10.1136/hrt.2007.125401. PMID 18480348. {{cite journal}}: Unknown parameter |month= ignored (help)
  19. ^ "Trans fat: Avoid this cholesterol double whammy". Mayo Foundation for Medical Education and Research (MFMER). Retrieved يونيو 25, 2010.
  20. ^ PMID 11864868 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  21. ^ PMID 11734581 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  22. ^ PMID 9719399 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  23. ^ PMID 7749823 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  24. ^ PMID 3987006 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  25. ^ PMID 3772283 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  26. ^ Hermansen K, et al. "Effects of soy and other natural products on LDL:HDL ratio and other lipid parameters: a literature review.", "National Institues of Health", 2003 Jan-Feb. Accessed 2011 May 31.
  27. ^ "The Power of Fish". The Cleveland Clinic Heart and Vascular Institute. Retrieved أكتوبر 8, 2009.
  28. ^ Mensink, Ronald P.; Zock, Peter L.; Kester, Arnold D. M.; Katan, Martijn B. (2003). "Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials". American Journal of Clinical Nutrition. 77 (5): 1146. PMID 12716665.
  29. ^ Thijssen, M.A. and R.P. Mensink. (2005). Fatty Acids and Atherosclerotic Risk. In Arnold von Eckardstein (Ed.) Atherosclerosis: Diet and Drugs. Springer. pp. 171–172. ISBN 9783540225690.
  30. ^ أ ب Soudijn, W; Van Wijngaarden, I; Ijzerman, AP (2007). "Nicotinic acid receptor subtypes and their ligands". Medicinal research reviews. 27 (3): 417–33. doi:10.1002/med.20102. PMID 17238156.
  31. ^ أ ب "NIH stops clinical trial on combination cholesterol treatment". National Institute of Health. National Heart, Lung, and Blood Institute (NHLBI). Retrieved يونيو 2, 2011.
  32. ^ Benatar, JR; Stewart, RA (2007). "Is it time to stop treating dyslipidaemia with fibrates?". The New Zealand medical journal. 120 (1261): U2706. PMID 17853928.
  33. ^ Meyers, CD; Kamanna, VS; Kashyap, ML (2004). "Niacin therapy in atherosclerosis". Current opinion in lipidology. 15 (6): 659–65. doi:10.1097/00041433-200412000-00006. PMID 15529025.
  34. ^ Rader, Daniel J. (2004). "Raising HDL in Clinical Practice". Raising HDL in Clinical Practice: Clinical Strategies to Elevate HDL. Retrieved أكتوبر 8, 2009.
  35. ^ أ ب Brewer, H. Bryan (ديسمبر 27, 2005). "Raising HDL-Cholesterol and Reducing Cardiovascular Risk: An Expert Interview With H. Bryan Brewer, Jr, MD". Retrieved أكتوبر 8, 2009.
  36. ^ Chapman, M. John; Assmann, Gerd; Fruchart, Jean-Charles; Shepherd, James; Sirtori, Cesare; European Consensus Panel on HDL-C (2004). "Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid – a position paper developed by the European Consensus Panel on HDL-C". Current medical research and opinion. 20 (8): 1253–68. doi:10.1185/030079904125004402. PMID 15324528.
  37. ^ Drexel, H. (2006). "Reducing risk by raising HDL-cholesterol: the evidence". European Heart Journal Supplements. 8: F23. doi:10.1093/eurheartj/sul037.
  38. ^ Meyers, C. Daniel; Carr, Molly C.; Park, Sang; Brunzell, John D. (2003). "Varying Cost and Free Nicotinic Acid Content in Over-the-Counter Niacin Preparations for Dyslipidemia". Annals of Internal Medicine. 139 (12): 996. PMID 14678919.
  39. ^ http://www.npr.org/blogs/health/2011/05/28/136678665/study-boosting-good-cholesterol-with-niacin-did-not-cut-heart-risks?ps=sh_sthdl
  40. ^ Rosanoff A, Seelig MS (2004). "Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals". J Am Coll Nutr. 23 (5): 501S–505S. PMID 15466951. HMG CoA Reductase is an important enzyme in lipid and cholesterol metabolism, but it is not the only one. The statins act by inhibiting, temporarily, the enzyme, in a dose response relationship whereas the magnesium ion (Mg2+) is an important part of a complex control and regulation of this important pathway. Both lower LDL-C, some statins can raise HDL-C and lower triglycerides, but Mg supplements do both quite reliably. {{cite journal}}: Unknown parameter |month= ignored (help)

وصلات خارجية

تمّ الاسترجاع من "https://www.marefa.org/w/index.php?title=پروتين_دهني_مرتفع_الكثافة&oldid=2891438"