Influence of sex hormones and phytoestrogens on heart disease in men and women.

Cardiovascular disease (CVD) is the number one cause of morbidity and mortality in men and women worldwide. According to the WHO, by 2015, almost 20 million people will die from CVD each year. It is well established that men and women differ not only in baseline cardiac parameters, but also in the clinical presentation, diagnosis and treatment outcomes of CVD.

Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes.

Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport. The inhibitory effect of SLN on cardiac SR Ca2+ ATPase (SERCA) pump can be relieved by beta-adrenergic stimulation, which indicates that SLN is a reversible inhibitor. However, the mechanism of this reversible regulation of SERCA pump by SLN is yet to be determined.

Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology.

Cardiac sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) plays a central role in myocardial contractility. SERCA2a actively transports Ca(2+) into the SR and regulates cytosolic Ca(2+) concentration, SR Ca(2+) load, and the rate of contraction and relaxation of the heart. In the heart, SERCA pump activity is regulated by two small molecular weight proteins: phospholamban (PLB) and sarcolipin (SLN).

Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility.

Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria. In this study we investigated the physiological significance of sarcolipin in the heart by generating a mouse model deficient for sarcolipin. The sarcolipin-null mice do not show any developmental abnormalities or any cardiac pathology.

Expression of SERCA isoform with faster Ca2+ transport properties improves postischemic cardiac function and Ca2+ handling and decreases myocardial infarction.

Myocardial ischemia-reperfusion (I/R) injury is associated with contractile dysfunction, arrhythmias, and myocyte death. Intracellular Ca(2+) overload with reduced activity of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) is a critical mechanism of this injury. Although upregulation of SERCA function is well documented to improve postischemic cardiac function, there are conflicting reports where pharmacological inhibition of SERCA improved postischemic function.

Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology.

Sarcolipin (SLN) is a small molecular weight sarcoplasmic reticulum (SR) membrane protein expressed both in cardiac and skeletal muscle tissues. Recent studies using transgenic mouse models have demonstrated that SLN is an important regulator of cardiac SR Ca2+ ATPase 2a (SERCA2a). However, there is a paucity of information regarding the SLN protein expression in small versus larger mammals and its regulation during development and cardiac pathophysiology.

Sarcolipin and phospholamban as regulators of cardiac sarcoplasmic reticulum Ca2+ ATPase.

The cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a critical role in maintaining the intracellular calcium homeostasis during cardiac contraction and relaxation. It has been well documented over the years that altered expression and activity of SERCA2a can lead to systolic and diastolic dysfunction. The activity of SERCA2a is regulated by two structurally similar proteins, phospholamban (PLB) and sarcolipin (SLN).

Targeted overexpression of sarcolipin in the mouse heart decreases sarcoplasmic reticulum calcium transport and cardiac contractility.

The role of sarcolipin (SLN) in cardiac physiology was critically evaluated by generating a transgenic (TG) mouse model in which the SLN to sarco(endoplasmic)reticulum (SR) Ca(2+) ATPase (SERCA) ratio was increased in the ventricle. Overexpression of SLN decreases SR calcium transport function and results in decreased calcium transient amplitude and rate of relaxation. SLN TG hearts exhibit a significant decrease in rates of contraction and relaxation when assessed by ex vivo work-performing heart preparations.