SNX17 produces anti-arrhythmic effects by preserving functional SERCA2a protein in myocardial infarction

Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion

“…SNX17 has previously been implicated in myocardial infarction. 21 The strongest eQTL detected in the GWASs of UACR and UK/UCr were for spermatogenesis associated 5 like 1 (SPATA5L1; rs60474696) and secretory carrier membrane protein 2 (SCAMP2; rs2472297) in cells transformed fibroblasts (P = 8.90 × 10 −49 ) and skin (P = 2.90 × 10 −9 ), respectively. The SPATA5L1 gene has previously been associated with CKD.…”

The emerging role of sorting nexins in cardiovascular diseases

“…Besides of the role of SNX in the pathogenesis of coronary artery disease, there is also evidence showing a role of SNX in the complications of coronary artery disease, especially in the ischemia-induced arrhythmia. In the ischemic myocardium, SNX17 is decreased, accompanied by cardiac electrical disturbances [92]. This is related to the finding that loss of SNX17 causes intracellular Ca 2+ overload as revealed by the abnormal rise of resting [Ca 2+ ] i and deceleration of decay of Ca 2+ transient indicative of sarcoplasmic reticulum Ca 2+ -ATPase2a (SERCA2a) dysfunction, whereas SNX17 overexpression produced the opposite effects [92].…”

“…In the ischemic myocardium, SNX17 is decreased, accompanied by cardiac electrical disturbances [92]. This is related to the finding that loss of SNX17 causes intracellular Ca 2+ overload as revealed by the abnormal rise of resting [Ca 2+ ] i and deceleration of decay of Ca 2+ transient indicative of sarcoplasmic reticulum Ca 2+ -ATPase2a (SERCA2a) dysfunction, whereas SNX17 overexpression produced the opposite effects [92]. SNX17, via its PX domain, also facilitates the lysosomal degradation of SERCA2a.…”

“Sorting” SERCA2a: A novel therapeutic strategy in heart failure?

“…During diastole, approximatively 70% of the Ca 2+ is actively sequestrated back into the SR via the sarco/endoplasmic reticulum Ca 2+ ATPase 2a (SERCA2a), or expelled from the cardiomyocytes by the Na + -Ca 2+ exchanger (NCX) pumps eventually leading to muscle relaxation. These tightly coordinated Ca 2+ handling processes are pivotal for cardiomyocytes achieving effective contraction, and dysregulation of any of the above Ca 2+ handling processes may result in heart failure (HF) and/or lethal cardiac arrhythmias [2]. Decreased SERCA2a levels and activity are proven to be one of the molecular determinants underlying the development of HF [3].…”

“…[7]. In this issue of International Journal of Cardiology , Zhao and colleagues demonstrated a novel mechanism - sorting nexin 17 (SNX17) mediated protein degradation of SERCA2a - could also contribute to the decreased SERCA2a protein levels in a rat model of myocardial infarction (MI) [2]. SNX17 is a member of large family of sorting nexins that function variously in pro-degradative sorting, internalization, endosomal recycling, or endosomal sorting [8].…”