Efforts to develop responses of greater potency and durability in this model are warranted. It is estimated that more than 12% of the US population will develop a thyroid condition during their lifetime, and an estimated 20 million Americans have already some form of thyroid disease. Besides, some of the most Carbimazole prominent and common symptoms of thyroid disease are those that result from the effects of thyroid hormone on the heart and cardiovascular system. Both hyperthyroidism and hypothyroidism produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance. Several important cardiac structural and functional proteins are transcriptionally regulated by thyroid hormones. The proteins that are positively regulated by thyroid hormones include sarcoplasmic reticulum VU 0364439 calcium ATPase that uptakes calcium into the sarcoplasmic reticulum during diastole, alpha myosin heavy chain the fast myosin with higher ATPase activity as well as beta adrenergic receptors, sodium/potassium ATPase and voltage-gated potassium channels which together coordinate the electrochemical responses of the myocardium; cardiac stress markers atrial and brain natriuretic peptides are also regulated by thyroid hormones. Other cardiac proteins are negatively regulated by thyroid hormones such as b-MHC the slow myosin, phospholamban the SERCA inhibitor and sodium/ calcium exchanger. Thus, changes in the amounts of these proteins account for the altered cardiac diastolic and systolic function induced by thyroid disease. Non-genomic effects are also exerted by thyroid hormones on cardiac myocytes and ion transport. In fact, triiodothyronine exerts effects on various sodium, potassium, and calcium channels in the heart, and thus changes in intracellular levels of calcium and potassium can increase inotropy and chronotropy. Hypertrophied and, in particular, failing hearts are characterized by an accumulation of extracellular matrix elements and a corresponding increase in cardiac muscle stiffness.