Table 2. Summary of SNX family and CVDs.
| SNX isoform | SNX modification | Effects of SNX modification on CVDs and related functions | Expression and function of SNX and SNX SNP in CVDs |
|---|---|---|---|
| SNX1 | SNX1 knockout | Elevates systolic and diastolic blood pressure, blunts natriuretic response to stimulation of D5R, increases the level of oxidative stress, and the expression of sodium transport including Na+,K+-ATPase, NHE3, and NCC [56]; increases levels of triglycerides and cholesterol (unpublished data). | Reduced SNX1 expression in human RPT cells of hypertensive Caucasian males compared with normotensive subjects [56]. |
| SNX1 knockdown | Increases the systolic and diastolic blood pressures in SNX1-depleted C57BL/6J mice and SNX1-depleted BALB/cJ mice; abrogates D5R-mediated cAMP production, GTP binding, and sodium transport inhibition [34]. | ||
| SNX3 | SNX3 overexpression | Increases ENaC levels in the total lysate and at the cell surface in mouse cortical collecting duct cells [67]. | None |
| SNX5 | SNX5 knockdown | Results in a further increase in systolic blood pressure and a decrease in sodium excretion in SHRs, and also increases blood insulin and glucose levels, decreases urinary insulin excretion, and causes insulin resistance in C57Bl/6J mice [33,55]; increases non-fasting serum insulin and glucose levels in WKY rats [55]; results in higher phosphorylation of D1R, impairment of D1R endocytosis, marked delay in receptor recycling, and failure of agonist-induced cAMP production [33]; decreases phosphorylations of insulin receptor and its substrate, protein kinase B phosphorylation [44]. | Reduced renal SNX5 expression in SHRs; decreased SNX5 expression in RPT cells of SHRs and hypertensive humans compared with WKY rats and normotensive subjects [55]. |
| SNX8 | SNX8 overexpression | Exacerbates aberrant handling of neuronal cholesterol [46]. | Reduced SNX8 expression after extreme changes in cholesterol such as treatment with mevinolin, a cholesterol-lowering statin [46]. |
| SNX9 | None | None | SNP rs2364349 in SNX9 is associated with changes in heart rate in response to β-blockers [99]. |
| SNX13 | SNX13 knockdown | Results in a markedly decrease in cardiac systolic function with striking cardiomyocyte apoptosis, facilitates the degradative sorting of apoptosis repressor with caspase recruitment domain [93]. | Reduced SNX13 expression in the failing hearts of humans and mouse model of heart failure [93]. |
| SNX17 | SNX17 overexpression | Promotes the endocytosis of P-selectin from the plasma membrane and inhibits the movement of P-selectin into lysosomes, thereby reducing its degradation in human umbilical vein endothelial cells [39]. | Decreased SNX17 expression in ischemic myocardium, accompanied with cardiac electrical disturbances [92]. |
| SNX19 | SNX19 knockdown | Increases blood pressure in C57Bl/6J mice; decreases D1R expression and its mediated-cAMP response, abrogates the D1R mediated-increased intracellular sodium in human RPT cells [57]; decreases insulin secretion and the number/size of dense core vesicles in mouse pancreatic β-cells [70]. | The SNP of SNX19 is associated with the incident of coronary artery disease in white participants of United States [79]; white participants with a high genetic risk score derived from combined multiple variants including SNX19 had a 57% increased risk of incident coronary artery disease [80]. |
| SNX24 | SNX24 knockdown | Decreases expressions of proinflammatory cytokines including IL-1β, IL-6, and IL-8 [89]. | Lesser coronary artery aneurysm complications in patients with CC + CT genotypes (rs28891) in SNX24 in Taiwanese children of Han Chinese ethnic background with Kawasaki disease [89]. |
| SNX25 | SNX25 overexpression | Enhances D1R and D2R expression and receptors-mediated signaling, perturbs both endocytosis and recycling of D2R [63]. | None |
| SNX25 knockdown | Decreases the D1R and D2R expression [64]. | ||
| SNX27 | SNX27 knockdown | Decreases GLUT4 expression [51]; inhibits recycling of β2AR [98]; decreases GLP-1R plasma membrane recycling, fails to sustain endosomal cAMP increases and reduces basal GLP-1R levels and increases exendin-4-induced receptor degradation in murine insulinoma MIN6B1 cells [78]; reduces exocytic insertion of NHE3 to the plasma membrane [66]. | None |
Abbreviations: β2AR, β2 adrenergic receptor; cAMP, cyclic adenosine monophosphate; CVD, cardiovascular disease; D1R, dopamine D1 receptor; D2R, dopamine D2 receptor; D5R, dopamine D5 receptor; ENaC, epithelial sodium channel; GLP-1R, glucagon-like peptide-1 receptor; GLUT4, glucose transporter isoform 4; GTP, guanosine triphosphate; HCTZ, hydrochlorothiazide; IL, interleukin; NCC, thiazide-sensitive sodium-chloride cotransporter; NHE3, sodium-hydrogen exchanger 3; RPT, renal proximal tubule; SHR, spontaneously hypertensive rat; SNP, single-nucleotide polymorphism; SNX, sorting nexin; WKY, Wistar-Kyoto.