thromboplastin and Hypertrophy

Tissue factor is the primary initiator of coagulation cascade and plays an essential role in haemostasis and thrombosis. In addition, tissue factor and coagulation proteases contribute to many cellular responses via activation of protease activated receptors. The heart is an organ with high levels of constitutive tissue factor expression. This review focuses on the role of tissue factor, coagulation proteases and protease activated receptors in heart haemostasis and the pathological heart remodelling associated with myocardial infarction, viral myocarditis and hypertension.

Topics: Animals; Blood Coagulation Factors; Fibrosis; Heart Valve Diseases; Hemostasis; Humans; Hypertension; Hypertension, Pulmonary; Hypertrophy; Models, Cardiovascular; Myocardial Infarction; Myocarditis; Myocytes, Cardiac; Receptors, Proteinase-Activated; Renin-Angiotensin System; Thromboplastin; Ventricular Remodeling

Hypertrophic adipocytes in obese states express the elevated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF). An increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP) promotes triglyceride hydrolysis and may improve dysregulation of adipocyte metabolism. Here, we investigate the effect of dibutyryl-cAMP (a phosphodiesterase-resistant analog of cAMP) on the gene expression of PAI-1 and TF in adipocytes.. Differentiated 3T3-L1 adipocytes were treated with dibutyryl-cAMP and agents that would be expected to elevate intracellular cAMP, including cilostazol (a phosphodiesterase inhibitor with anti-platelet and vasodilatory properties), isoproterenol (a beta adrenergic agonist) and forskolin (an adenylyl cyclase activator). The levels of PAI-1 and TF mRNAs were measured using real-time quantitative reverse transcription-PCR.. The treatment of adipocytes with dibutyryl-cAMP resulted in the inhibition of both lipid accumulation and TF gene expression. However, PAI-1 gene expression was slightly but significantly increased by dibutyryl-cAMP. On the other hand, cilostazol inhibited the expression of PAI-1 without affecting lipid accumulation. When the adipocytes were treated with cilostazol in combination with isoproterenol or forskolin, the inhibitory effect of cilostazol on PAI-1 gene expression was counteracted, thus suggesting that inhibition by cilostazol may not be the result of intracellular cAMP accumulation by phosphodiesterase inhibition. These results suggest the implication of cAMP in regulation of the gene expression of TF and PAI-1 in adipocytes. Our findings will serve as a useful basis for further research in therapy for obesity-associated thrombosis.

Topics: 3T3-L1 Cells; Adenylyl Cyclases; Adipocytes; Adrenergic beta-Agonists; Animals; Bucladesine; Cilostazol; Colforsin; Cyclic AMP; Enzyme Activation; Enzyme Activators; Gene Expression Regulation; Hypertrophy; Isoproterenol; Lipid Metabolism; Mice; Phosphodiesterase Inhibitors; Plasminogen Activator Inhibitor 1; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tetrazoles; Thromboplastin