An Overview of the Role of Calcium/Calmodulin-Dependent Protein Kinase in Cardiorenal Syndrome

Abstract

Calcium/calmodulin-dependent protein kinases (CaMKs) are key regulators of calcium signaling in health and disease. CaMKII is the most abundant isoform in the heart; although classically described as a regulator of excitation-contraction coupling, recent studies show that it can also mediate inflammation in cardiovascular diseases (CVDs). Among CVDs, cardiorenal syndrome (CRS) represents a pressing issue to be addressed, considering the growing incidence of kidney diseases worldwide. In this review, we aimed to discuss the role of CaMK as an inflammatory mediator in heart and kidney interaction by conducting an extensive literature review using the database PubMed. Here, we summarize the role and regulating mechanisms of CaMKII present in several quality studies, providing a better understanding for future investigations of CamKII in CVDs. Surprisingly, despite the obvious importance of CaMKII in the heart, very little is known about CaMKII in CRS. In conclusion, more studies are necessary to further understand the role of CaMKII in CRS.

The Organizer and Its Signaling in Embryonic Development

“…The intracellular Ca 2+ concentration is directly modulated by influx (from the extracellular space or endoplasmic reticulum), mediated via several types of Ca 2+ channels. The intracellular Ca 2+ interacts with and activate a variety of calcium-binding effector proteins (e.g., Calmodulin (CaM)) and Ca 2+ -dependent protein kinase (CDPK) [ 67 , 68 , 69 ]. Collectively, CaM and CDPK activate several sets of other CaM kinases (CaMKs); once CaMKs are activated, they can modulate several other intermediate signaling molecules ( Figure 2 D) and transcription factors to regulate cell fate and differentiation [ 67 , 68 , 69 , 70 ].…”

“…The intracellular Ca 2+ interacts with and activate a variety of calcium-binding effector proteins (e.g., Calmodulin (CaM)) and Ca 2+ -dependent protein kinase (CDPK) [ 67 , 68 , 69 ]. Collectively, CaM and CDPK activate several sets of other CaM kinases (CaMKs); once CaMKs are activated, they can modulate several other intermediate signaling molecules ( Figure 2 D) and transcription factors to regulate cell fate and differentiation [ 67 , 68 , 69 , 70 ]. In recent years, many important reports have demonstrated that Ca 2+ is essential for involuting/migrating mesodermal cells [ 71 , 72 ].…”

Polymorphism rs7214723 in CAMKK1: a new genetic variant associated with cardiovascular diseases

“…Genetic variants in eNOS have been associated with low nitric oxide concentrations and vascular density [32][33][34][35]. Among these genes, the calcium/calmodulin kinase family proteins represent a group of genes particularly associated with CVDs [24,36,37]. Among them, CAMK2 is the most studied in the contest of the physiology of the heart [38][39][40].…”

“…Among these genes, the calcium/calmodulin kinase family proteins represent a group of genes particularly associated with CVDs [ 24 , 36 , 37 ]. Among them, CAMK2 is the most studied in the contest of the physiology of the heart [ 38–40 ].…”

Ca2+/calmodulin-dependent Protein Kinases in Leukemia Development

“…Calcium (Ca 2+ ) is an intracellular universal second messenger that regulates a variety of cellular processes. Many biological processes, including gene transcription, cell cycle, migration, and apoptosis, are affected by changes in intracellular Ca 2+ signaling [ 1 , 2 ]. Disruption of normal Ca 2+ signaling can cause tumorigenic phenotypes [ 3 ].…”