Triglyceride

Triglyceride (veraltet auch Triglyzeride) sind dreifache Ester des dreiwertigen Alkohols Glycerin mit drei Säuremolekülen. Handelt es sich dabei um Carbonsäuren sollten die Verbindungen nach der IUPAC-Empfehlung besser als Triacylglycerine (TAG) bezeichnet werden. Triacylglycerine mit drei Fettsäuren sind die Verbindungen in Fetten und fetten Ölen. Phosphoglyceride wie z.B. Lecithine sind Triglyceride aus zwei Fettsäuren und einer organischen Phosphorsäureverbindung. Beide Verbindungstypen zählen zur Klasse der Lipide. Neben pflanzlichen und tierische Triglyceriden gibt es auch synthetische Triglyceride.
Natürliche Fette bestehen zum überwiegenden Teil aus Triglyceriden mit drei langkettigen Fettsäuren, die meist aus unverzweigten Ketten mit 4 bis 26, typischerweise 12 bis 22 Kohlenstoff-Atomen bestehen. Sind sie bei Raumtemperatur flüssig, werden sie auch als Öle oder, um sie von den Mineralölen zu unterscheiden, fette Öle bezeichnet. Reine Triacylglycerine von Fettsäuren werden auch als Neutralfette bezeichnet. Die einzelnen Verbindungen unterscheiden sich durch die beteiligten Fettsäuren. Sind die Reste R an den Kohlenstoffatomen 1 und 3 unterschiedlich, ist das Molekül chiral und damit optisch aktiv.
Der Normwert liegt beim Menschen unter 180 mg/dl bzw. unter 2 mmol/l. Ein erhöhter Wert findet sich bei verschiedenen Erkrankungen und wird unter Hypertriglyceridämie beschrieben.

D-4F

APP018 (formerly D-4F), an 18-amino acid peptide (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2[10][11], using D-amino acids) that can be taken orally, was developed by Bruin Pharmaceuticals (a little-known company founded by Dr. Alan Fogelman, named after the UCLA Bruins[12][13]) and sold to Novartis for $200 million USD. The peptide and close variations thereof such as D-5F have been shown to elevate HDL-C and reduce atherosclerotic build-up in early animal data. The peptide has been tested with a variety of modifications, formulated with an excipient such as poly(lactide-co-glycolide) (PLG), and formed into ProLease[14] drug-polymer microspheres. If all continues to go well it is expected to reach the pharmacy shelf around 2013.[15] A G/A polymorphism[disambiguation needed] in the promoter of the ApoA-I gene has been associated with the age at which patients presented with Alzheimer disease.[16] Protection from Alzheimer disease by ApoA1 may rely on a synergistic interaction with alpha-tocopherol[17]. Amyloid deposited in the knee following surgery consists largely of ApoA-I secreted from chondrocytes (cartilage cells).[18] A wide variety of amyloidosis symptoms are associated with rare ApoA-I mutants. ApoA-I binds to lipopolysaccharide or endotoxin, and has a major role in the anti-endotoxin function of HDL.[19] — In contrast to D-4F, D- [113–122]apoJ showed minimal self-association and helicity in the absence of lipids. D-4F increased the concentration of apoA-I with pre-ß mobility in apoE-null mice whereas D- [113–122]apoJ did not. After an oral dose D- [113–122]apoJ more slowly associated with lipoproteins and was cleared from plasma much more slowly than D-4F. D- [113–122]apoJ significantly improved the ability of plasma to promote cholesterol efflux and improved high-density lipoprotein (HDL) inflammatory properties for up to 48 hours after a single oral dose in apoE-null mice, whereas scrambled D- [113–122]apoJ did not. Oral administration of 125 µg/mouse/d of D- [113–122]apoJ reduced atherosclerosis in apoE-null mice (70.2% reduction in aortic root sinus lesion area, P=4.3x10–13; 70.5% reduction by en face analysis, P=1.5x10–6). In monkeys, oral D- [113–122]apoJ rapidly reduced lipoprotein lipid hydroperoxides (LOOH) and improved HDL inflammatory properties. Adding 250 ng/mL of D-[113–122]apoJ (but not scrambled D- [113–122]apoJ) to plasma in vitro reduced LOOH and increased paraoxonase activity. Conclusions— Oral D- [113–122]apoJ significantly improves HDL inflammatory properties in mice and monkeys and inhibits lesion formation in apoE-null mice. Oral D- [113–122]apoJ, a peptide synthesized from D-amino acids corresponding to residues 113 to 122 in apolipoprotein J, significantly improves HDL inflammatory properties in mice and monkeys and inhibits lesion formation in apoE-null mice.

Arteriosclerosis

Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (in Greek, "Arterio" meaning artery and "sclerosis" meaning hardening). Arteriosclerosis results from a deposition of tough, rigid collagen inside the vessel wall and around the atheroma

Atherosclerosis

Atherosclerosis is is a chronic inflammatory response in the walls of arteries, in large part to the deposition of lipoproteins It is commonly referred to as a "hardening" or "furring" of the arteries. It is caused by the formation of multiple plaques within the arteries.
Pathologically, the atheromatous plaque is divided into three distinct components:
The atheroma ("lump of porridge", from Athera, porridge in Greek,) is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery.
Underlying areas of cholesterol crystals.
Calcification at the outer base of older/more advanced lesions.
The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused: arteriosclerosis, arteriolosclerosis and atherosclerosis. Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries.
Atherosclerosis causes two main problems. First, the atheromatous plaques, though long compensated for by artery enlargement, see IMT, eventually lead to plaque ruptures and stenosis (narrowing) of the artery and, therefore, an insufficient blood supply to the organ it feeds. Alternatively, if the compensating artery enlargement process is excessive, then a net aneurysm results.
These complications are chronic, slowly progressing and cumulative. Most commonly, soft plaque suddenly ruptures (see vulnerable plaque), causing the formation of a thrombus that will rapidly slow or stop blood flow, e.g. 5 minutes, leading to death of the tissues fed by the artery. This catastrophic event is called an infarction. One of the most common recognized scenarios is called coronary thrombosis of a coronary artery causing myocardial infarction (a heart attack). Another common scenario in very advanced disease is claudication from insufficient blood supply to the legs, typically due to a combination of both stenosis and aneurysmal segments narrowed with clots. Since atherosclerosis is a body wide process, similar events also occur in the arteries to the brain, intestines, kidneys, legs, etcmethods during life. Autopsies of healthy young men who died during the Korean and Vietnam Wars showed evidence of the disease. It most commonly becomes seriously symptomatic when interfering with the coronary circulation supplying the heart or cerebral circulation supplying the brain, and is considered the most important underlying cause of strokes, heart attacks, various heart diseases including congestive heart failure and most cardiovascular diseases in general. Atheroma in arm or more often leg arteries and producing decreased blood flow is called Peripheral artery occlusive disease (PAOD).
According to United States data for the year 2004, for about 65% of men and 47% of women, the first symptom of atherosclerotic cardiovascular disease is heart attack or sudden cardiac death (death within one hour of onset of the symptom).
Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average. [The reader might reflect that the illustration above, like most illustrations of arterial disease, over emphasizes lumen narrowing as opposed to compensatory external diameter enlargement (at least within smaller, e.g. heart arteries) typical of the atherosclerosis process .