Csk Regulates Blood Pressure by Controlling the Synthetic Pathways of Aldosterone

Abstract

represent extreme cases, because most hypertensive cases are not explained by a mutation in a single gene. 3 Further, the finding of genes that cause monogenic syndromes highlights the significant functions of the kidney and adrenal gland in regulating blood pressure. 2,3 Specifically, 10% of all monogenic forms of hypertension are estimated to have primary aldosteronism, suggesting that the homeostatic maintenance of aldosterone levels and the effect of aldosterone on kidney function are pivotal in keeping blood pressure within the normal range. 3 Despite the increase in the discoveries of SNPs that are associated with blood pressure, few cases have revealed an association between a genetic variation and the causal pathway that leads to hypertension. The most notable studies have reported a variant (rs13333226) in the promoter region of the uromodulin gene (UMOD), 8 a SNP in the promoter (rs3918226) near the endothelial nitric oxide synthase (eNOS) gene, 9,10 a SNP (rs5068) in the 3' untranslated region of NPPA, the gene that encodes for atrial natriuretic peptide (ANP), 11,12 and a SNP (rs17249754) B lood pressure is a complex trait that is regulated by a network of physiological pathways that involve the modulation of heart rate, vascular tone, and blood volume. 1 Short-term regulation of blood pressure is attained via the effects of sympathetic/parasympathetic activation on vascular tone and cardiac contractility through the sensing of baroreceptors in large arteries, whereas longterm regulation occurs through the effects of the reninangiotensin-aldosterone system (RAAS) on the kidney in controlling blood volume. 2 Despite their classical definition, short-term regulatory mechanisms are not easily dissected from long-term mechanisms, because the autonomic nervous system and RAAS permeate common target tissues and often relay signals through shared signaling pathways.Genetic research, including genome-wide association studies (GWASs), has identified approximately 116 singlenucleotide polymorphisms (SNPs) and rare mutations that contribute to the genetic architecture of blood pressure and hypertension. 3-7 It is now evident that hypertension is a polygenic trait, wherein rare syndromes of hypertension Background: Blood pressure is regulated by a network of diverse physiological pathways. The C-terminal Src kinase (CSK) locus (15q24) is associated with blood pressure in various ethnic groups. It was recently reported that Csk insufficiency increases blood pressure through Src. The mechanisms of hypertension in Csk +/− mice are examined further in this study.

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

“… 34 ). Lower DNAm at cg26843110 associated with shorter GA at birth, and decreased expression of CSK , which is involved in trophoblast differentiation 43 , as well as blood pressure and aldosterone regulation 44 . Finally, cg17823829 (annotated to KDM5B ) was hypermethylated with MSDP.…”

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

“…We also observed lower DNAm with MSDP at cg26843110, which is within the body of the EDC3 gene, and is nearby to SNPs associated with BW (rs3784789 31 ). Lower DNAm at cg26843110 associated with shorter GA at birth, and decreased expression of CSK , which is involved in trophoblast differentiation 40 as well as blood pressure and aldosterone regulation 41 . Finally, cg17823829 (annotated to KDM5B ) was hypermethylated with MSDP.…”

Src-family Protein Tyrosine Kinases: A promising target for treating Cardiovascular Diseases

“…Blood pressure is a complex network regulated by a series of physiological pathways. It is reported that the C-terminal Src kinase (Csk) works as a negative regulator of SFKs and a core modulator of blood pressure physiologically via inhibiting the adrenal gland to synthesize more aldosterone, regulating the contraction, growth and migration of VSMs, changing in the blood volume and sodium absorption, ultimately affects blood pressure levels [32,33]. And it has been confirmed that gene silencing and Haploinsufficiency of Csk could increase blood pressure via up-regulating the active form of Src [34].…”