Cardiovascular Disease

Hypertension is a major risk factor for cardiovascular disease. ER stress has been shown to increase production of endothelium-derived contractile factors (EDCFs), such as vasoconstrictor prostanoids that increase resistance, resulting in hypertension.TUDCA treatment in rats for 1 week showed decreased signs of ER stress such as expression of COX-1 and
kinase phosphorylation and decreased levels of prostanoids and blood pressure. TUDCA also decreased activation of transcription factor 6 and ameliorated the decrease in mitochondrial calcium in rats with hypertension. It also suppressed proliferation in pulmonary artery smooth muscle cells and reduced the elevated blood pressure. TUDCA injections into the lateral cerebroventricles of mice reduced ER stress in the brain
and its associated Ang II-dependent hypertension.Contractile function is critical to the function of the heart.Up-regulation of the SERCA2a protein
increased LV diastolic dysfunction in rats, and this was almost entirely reversed with TUDCA treatment in diabetic rats.ER stress induces cardiomyoctye contractile dysfunction and is associated with intracellular
Ca2+ defects, which improved upon treatment with TUDCA. One study also showed TUDCA can promote cardioprotection through the prevention of ER stress,which inhibits erythropoietin-induced suppression of
mitochondrial permeability transition pore opening. In additional cardiac studies, TUDCA was able to oxidize low-density lipoprotein deposition and reduce AVcalcification, inhibit neointimal hyperplasia and the proliferation of vascular smooth muscle cells (VSMCs), and significantly reduce the injury from myocardial infarction.These improvements result from the myriad of mechanisms described above, including
mitochondrial protection and reduction in ER stress.