Thromboxane synthase expression and thromboxane A2 production in the atherosclerotic lesion

Abstract

Thromboxane A(2) (TXA(2)) is a potent prothrombotic and immune modulating lipid mediator, which is implicated in cardiovascular diseases, in particular, atherosclerotic lesion development and thrombogenicity. Here, we tested the hypothesis that thromboxane synthase (TXAS), the obligate enzyme required to synthesize TXA(2), is expressed within the human atherosclerotic lesion, thus potentially contributing to TXA(2) synthesis and disease development. In an animal study, different atherosclerosis-prone mouse strains were investigated and compared with control mice. In a patient study (n = 134), endarterectomies of carotid atherosclerotic lesions were compared with non-atherosclerotic arteries (n = 11). Expression of TXAS was evaluated by real-time quantitative reverse transcription PCR and immunohistochemistry. TXAS mRNA expression was increased within the vascular wall in mouse models of atherosclerosis with advanced lesions. In humans, TXAS was expressed in the atherosclerotic lesion, associated with increased inflammatory cells, in particular M2 polarized macrophages, and increased in atherosclerotic lesions of patients with recent symptoms of thrombotic events. Production of TXA(2) by plaque tissue, verified by gas chromatography-mass spectrometry, increased after addition of arachidonic acid or lipopolysaccharide, and was inhibited by the TXAS inhibitor furegrelate. The findings suggest that intraplaque TXA(2) generation may contribute to the development of atherosclerosis and its thrombotic complications in humans.

Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

“…PAD is an inflammatory condition [39] which is known to promote COX 2 activity [40] and the abundance of atherosclerotic lesions in the vasculature has been directly linked to elevated concentrations of the potent vasoconstrictor, thromboxane [41]. We did not find a difference between groups in enzyme levels of thromboxane synthase, COX 1 or COX 2.…”

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

“…Newly formed platelets beside their constitutive cyclooxygenase (COX)‐1 expression, retain COX‐2 activity contributing to additional TX synthesis 1, 2, 11, 20, 21. Further, intense thrombotic and concomitant acute inflammatory processes present in AMI induce TX synthesis from sources other than platelets, mostly inflammatory (monocytes and macrophages) and endothelial cells 22. These cells produce TX mainly via the COX‐2 pathway and stimulate platelets despite their inhibition by aspirin 23.…”

Meat nutritional composition and nutritive role in the human diet

“…Meat is an important arachnidonic acid source, an omega 6 polynsaturated fatty acid which increases the risk of thrombosis (Christophersen & Haug, 2011;Mann, Johnson, Warrick, & Sinclair, 1995). Arachidonic acid is the precursor of thromboxane A 2 which begins plaque aggregation, the primary phenomena in thrombosis development (Gabrielsen et al, 2010). Arterial thrombosis influences the evolution from a stable form of isquemic cardiac disease to an acute phase, shown by an unstable angina which can lead to myocardial disease and in sudden death (Libby, Ridker, & Hansson, 2009).…”