Prostacyclin in Human Physiology
Creation and Protective Properties of PGI2
Prostacylin is a local-acting cellular messenger that appears to protect the cardiovascular system and inhibit inflammation. This article will briefly explore the properties of this interesting eicosanoid.
The Basics
Scientific nomenclature: (Z)-5-[(4R,5R)-5-hydroxy-4-(S,E)-3-hydroxyoct-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid
MW: 352.465 grams/mol Formula: C20H32O5 Abbreviation: PGI2
Eicosanoids
Prostacyclin is an extensively studied member of a family of molecules called eicosanoids. These are lipid molecules containing twenty carbons. Within the eicosanoid family, these carbons are arranged by enzymes to create three distinct classes: prostaglandins, leukotrienes, and thromboxanes. They are all signaling molecules that act locally and have a brief effect compared to conventional endocrine-produced hormones.
Prostacyclin
Prostacyclin is a special prostaglandin eicosanoid that prevents clotting and induces the dilation of blood vessels. It unifies and strengthens contractions during pregnancy and decreases tumor growth in some forms of cancer. It also appears to exert a protective action against allergic inflammation by decreasing the ability of inflammatory white blood cells to attach and move between the endothelial tissue lining blood vessels.
Prostacyclin is not stored, instead it is created on-demand by endothelial cells that line blood vessels. Enzymatic reactions cause arachidonic acid (an omega-6 poly unsaturated fatty acid) to be cleaved from either the nuclear or cell membrane. This lipid is then processed by the infamous cyclooxygenase enzymes (COX 1&2) into an intermediary prostaglandin (PGH2) -which is finally converted to prostacyclin by an enzyme fittingly called prostacyclin synthase. When prostacyclin is released from cells it acts locally on other endothelial tissue and nearby platelets to increase circulation and decrease clotting. Prostacyclin is quickly broken down enzymatically to 6-keto-PGF1.
Homeostatic Actions
Studies indicate that prostacyclin is continually released from circulatory tissues of the blood vessels and heart, helping to maintain optimal blood flow. This is in opposition to another eicosanoid released by cell fragments in the blood (platelets) called thromboxane A2 (TXA2) that promotes clotting (thrombosis), vasoconstriction, and blood pressure elevation. It appears that these two eicosanoids continually oppose each other, creating a dynamic balance to regulate blood circulation.
Medications
Several types of medication strategies have been utilized to address inflammatory states and reduce pain. Prostacyclin synthesis may be affected in several ways. Corticosteroids like prednisone reduce eicosanoid production by depriving COX enzymes the material (lipids) needed for their creation. Non steroidal anti-inflammatory medications (NSAIDS) like aspirin, block the function of COX enzymes so eicosanoids of the prostaglandin and thromboxane classes are not created. COX-2 inhibitors (celecoxib aka Celebrex) selectively block the production of prostacyclin and other prostaglandins. At first this was thought to be a good thing, because many eicosanoids of the 2-series are pro-inflammatory. But, after cardiovascular-related deaths increased in those taking COX-2 inhibitors it was realized that the circulatory system was being stripped of important protective factors like prostacyclin.
Natural Factors
Generally, prostacyclin is created from an arachidonic acid, omega-6 source. When more omega-3s are incorporated in the diet, a special type of prostacyclin called PGI3 is created -which is even more protective. High omega-3 intake also shunts production away from the creation of other inflammatory prostaglandins and thromboxanes. This inhibits the clotting of blood so those already on anticoagulation therapy (like warfarin/coumadin) should avoid omega-3 supplementation unless doctor-supervised. Substances like ursolic and oleanolic acid, compounds found in many medicinal herbs, have the ability to modulate COX enzymes to create less of the inflammatory signallers, while increasing prostacyclin.
Supplemental Resource
Fetalvero, K.M., Peisheng, Z., Shyu, M., 2008. Prostacycline Primes Pregnant Human Myometrium for an Enhanced Contractile Response in Parturition. J. Clin. Investigation. doic:10.1172/JCI33800.
Guyton & Hall, Textbook of Medical Physiology, 11th ed., Elsevier
Martinez-Gonzalez, J. Rodriguez, R. 2008. Oleanolic Acid Induces Prostacyclin Release in Human Vascular Smooth Muscle Cells through a Cyclooxygenase-2-Dependent Mechanism. Journal of Nutrition. 138:443-448.
Nigam, S., Zakrzewicz, S. 1992. Clinical Significance of Prostacyclin and Thromboxane in Cancer of the Female Breast and Genital Tract. Cancer and Metastasis Reviews 11: 411-420.
Rakoth-Nahoun, 2007. Prostaglandin-Secreting Cells: A Portable First Aid Kit for Tissue Repair. Journal of Clin Investigation. Volume 117, No. 1.
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