3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors

Randomized controlled clinical studies have suggested 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in both primary and secondary prevention of cardiovascular disease (CVD) events.1 Primary prevention refers to interventions that obviate the first occurrence of a disease or condition, secondary interventions deter reoccurrence.

The use of statins for primary intervention is extensive for individuals with no previous CVD but who have both elevated cholesterol levels and high blood pressure, or individuals who have coronary heart disease plus multiple risk factors such as diabetes and high blood pressure.2

While cholesterol has been singled out as the primary factor in the development of atherosclerosis, some research studies suggest that C-reactive protein (CRP) may also be a marker for the development and progression of atherosclerosis.3-5 Elevated basal levels of CRP can lead to inflammation of arterial vessels, increasing the risk of hypertension and cardiovascular disease.4

In 2010, rosuvastatin was approved in the U.S. to prevent CVD in individuals over 50 with normal low density lipid (LDL)-cholesterol levels and no history of heart disease, but elevated CRP levels coupled with one other risk factor such as high blood pressure.6

You can obtain seven statins from Sigma® Life Science, including the two drug candidates, mevastatin (M2537) and SR 12813 (S4194). We also offer complementary products such as antibodies, biomolecules, and zinc finger nucleases. Visit sigma.com to discover all the products relevant to your research.

HMG-CoA References

1.
Pichandi et al. 2011. The role of statin drugs in combating cardiovascular diseases.. Int J Cur Sci Res. 147-56.
2.
Glueck C, Goldenberg N. Efficacy, effectiveness and real life goal attainment of statins in managing cardiovascular risk. VHRM.369. http://dx.doi.org/10.2147/vhrm.s3241
3.
Kleemann R, Kooistra T. 2005. HMG-CoA Reductase Inhibitors: Effects on Chronic Subacute Inflammation and Onset of Atherosclerosis Induced by Dietary Cholesterol. CDTCHD. 5(6):441-453. http://dx.doi.org/10.2174/156800605774962077
4.
Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V. 2004. C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease. N Engl J Med. 350(14):1387-1397. http://dx.doi.org/10.1056/nejmoa032804
5.
Levinson SS. 2006. Inflammatory and Long-term Risk Markers. Clinics in Laboratory Medicine. 26(3):553-570. http://dx.doi.org/10.1016/j.cll.2006.06.001
6.
MacDonald G. 2010. Cost-effectiveness of rosuvastatin for primary prevention of cardiovascular events according to Framingham risk score in patients with elevated C-reactive protein.. J Am Osteopath Assoc. 110427-36.

Peroxisome Proliferator-Activated Receptor (PPAR) Agonists

Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors that function as transcription factors on targeted genes when heterodimerized with the retinoid X receptor.1

PPAR-α is mainly involved in fatty acid oxidation and is expressed in the liver, kidney, and skeletal muscle, while PPAR-γ is primarily involved in fat cell differentiation and insulin sensitivity.2 Both are expressed in smooth muscle cells and myocardium.

PPAR agonists have been shown to reduce blood pressure in several models of hypertension, correct endothelial dysfunction, and exert anti-inflammatory actions.3-5 Therefore, these therapeutic agents are used to prevent vascular and cardiac complications associated with hypertension.

PPAR References

1.
Francis G. 2003. PPAR agonists in the treatment of atherosclerosis. Current Opinion in Pharmacology. 3(2):186-191. http://dx.doi.org/10.1016/s1471-4892(03)00014-6
2.
Calkin AC, Thomas MC. 2008. PPAR Agonists and Cardiovascular Disease in Diabetes. PPAR Research. 20081-12. http://dx.doi.org/10.1155/2008/245410
3.
Buchan K, Hassall D. 2000. PPAR agonists as direct modulators of the vessel wall in cardiovascular disease.. Med Res Rev. 20350-66.
4.
Inoue I, Shino K, Noji S, Awata T, Katayama S. 1998. Expression of Peroxisome Proliferator-Activated Receptor ? (PPAR?) in Primary Cultures of Human Vascular Endothelial Cells. Biochemical and Biophysical Research Communications. 246(2):370-374. http://dx.doi.org/10.1006/bbrc.1998.8622
5.
Vu-Dac N, Chopin-Delannoy S, Gervois P, Bonnelye E, Martin G, Fruchart J, Laudet V, Staels B. 1998. The Nuclear Receptors Peroxisome Proliferator-activated Receptor ? and Rev-erb? Mediate the Species-specific Regulation of Apolipoprotein A-I Expression by Fibrates. J. Biol. Chem.. 273(40):25713-25720. http://dx.doi.org/10.1074/jbc.273.40.25713

Acyl–Coenzyme A:Cholesterol Acyltransferase (ACAT) Inhibitors

The enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol in a variety of tissues. In some animal models, ACAT inhibitors act alone or in combination with HMG-CoA inhibitors to exert their antiatherosclerotic effects.1 This effect is presumed to occur through the regulation of cholesterol trafficking pathways in the liver and vascular cells.2

ACAT References

1.
Nissen SE, Tuzcu EM, Brewer HB, Sipahi I, Nicholls SJ, Ganz P, Schoenhagen P, Waters DD, Pepine CJ, Crowe TD, et al. 2006. Effect of ACAT Inhibition on the Progression of Coronary Atherosclerosis. N Engl J Med. 354(12):1253-1263. http://dx.doi.org/10.1056/nejmoa054699
2.
Bocan TM, Bak Mueller S, Quenby Brown E, Lee P, Bocan MJ, Rea T, Pape ME. 1998. HMG-CoA reductase and ACAT inhibitors act synergistically to lower plasma cholesterol and limit atherosclerotic lesion development in the cholesterol-fed rabbit. Atherosclerosis. 139(1):21-30. http://dx.doi.org/10.1016/s0021-9150(98)00046-x

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