ReviewProstanoids in the pathophysiology of human coronary artery
Introduction
Coronary arteries play a critical role in the supply of blood flow to the myocardium. When the plaque builds up inside the coronary artery, blood flow is partially or totally blocked. This change is named by atherosclerosis and it is the main common reason for coronary artery disease (CAD). This disease has severe implications by decreasing the supply of oxygen and nutrients to the myocardium and may result in myocardial infarction [1]. Several endogenous factors are implicated in the development or progression of CAD, among them prostanoids could be important key elements because of their substantial involvements in the physiology and pathophysiology of the coronary artery.
Prostanoid synthesis is initiated by arachidonic acid release from phospholipids by the action of phospholipase A2 (PLA2) enzymes in the cell membrane. Then arachidonic acid is converted to prostaglandin (PG)H2 via cyclooxygenases (COX-1 and COX-2) enzymes. PGE2, prostacyclin (PGI2), PGD2, PGF2α and thromboxane A2 (TxA2) are formed from PGH2 via prostanoid synthase enzymes. The prostanoids are involved in vascular homeostasis by regulating vascular wall remodelling and muscular tone [2], [3]. Basically, the vascular wall produces mainly the vasodilator and antiplatelet prostanoid PGI2, while blood components such as platelets release the vasoconstrictor and proaggregant prostanoid TxA2. However, increasing evidences demonstrate synthesis and roles for PGE2 in the cardiovascular system [3], [4]. Interactions between the vascular wall and blood cells could be maintained by the balance between detrimental and beneficial prostanoids in physiological conditions [5]. However, this balance in prostanoid release is impaired in pathophysiological conditions such as CAD. For this reason, the prostanoids could have important impacts on the prevention or treatment of CAD. In fact, emerging evidence on the impact of the prostanoids in coronary artery physiology is strongly suggested by numerous clinical studies concerning both the beneficial effects of aspirin administration in the post-operative period of coronary artery bypass grafting (CABG) surgery [6] and the cardiovascular side effects (such as myocardial infarction) induced by COX-2 inhibitors or NSAIDs (non-steroidal anti-inflammatory drugs) [7]. In this review, we focused on the role of prostanoids in the regulation of human coronary artery homeostasis (vascular tone and wall remodelling) and their involvements in the development of CAD are addressed.
Section snippets
In healthy condition
In normal conditions without inflammatory stimuli, only COX-1 is detectable by western blot and/or RT-PCR analysis in cultured human coronary artery endothelial cells (HCAEC) [8], [9] or smooth muscle cells (HCASMC) [10], [11]. Respective synthase enzymes for PGI2, TxA2 or PGE2 have been detected in HCAEC [9]. In addition, in isolated fresh human coronary artery, the production of all major prostanoids (PGI2, TxA2, PGD2, PGF2α, PGE2, PGE1) has been confirmed by radioimmunoassay [12].
Regulation of vascular tone by prostanoids in vitro
Prostanoids are implicated in the regulation of human vascular tone by activating their specific receptors. When these receptors are localized on the smooth muscle, classically the activation of IP, EP2, EP4 or DP receptors by prostanoids induces vasodilatation, while the activation of TP, EP1, EP3, or FP receptors is responsible for vasoconstriction [2]. Control of vascular tone by prostanoids in human coronary artery could be differently regulated depending on the stimulus (agonist, hypoxia,
Prostanoids in coronary artery disease
Alterations of prostanoid productions and their synthase enzymes in CAD or related conditions are summarised in Table 2. In vitro expression of COX-2 has been detected in smooth muscle and endothelial cells of atherosclerotic human coronary artery [66], [67]. In addition, during myocardial ischemia, COX-2 mRNA and protein expressions have increased while COX-1 and PGIS levels remain unchanged in human coronary arterioles [68]. Similar results have been obtained by in vivo studies showing that
Conclusions
The mechanism underlying coronary artery diseases is dependent on the interactions between blood cells and coronary artery vascular wall. The roles of prostanoids on platelet aggregation/thrombosis and consequently their involvements in CAD are widely documented in literature. However, there is limited data concerning the effects of prostanoids on the coronary artery vascular wall and most of them were derived from animal studies. The studies performed in human coronary artery preparations
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