Ca2+/Calmodulin-Dependent Protein Kinases: Role In Excessive Cell Growth And Hypertension

Abstract

Hypertension is a widespread disease with over one-third of all US citizens being afflicted. Hypertension significantly increases the likelihood of heart disease, which is the currently leading cause of death in the US. This paper reviews the factors that cause hypertension, such as increased cardiac output, increased stroke volume, increased vessel length, and decreased vessel radius. The second section delves into our research on how excessive pulmonary arterial smooth muscle cell (PASMC) proliferation contributes to hypertension. We observed that patients with idiopathic pulmonary arterial hypertension (IPAH) have increased cytosolic calcium concentration in their PASMCs. However, it is unknown how calcium plays a role in this increased proliferation. This study explores our hypothesis that the family of proteins Ca2+/Calmodulin-Dependent Protein Kinases (CaMK) may be the link between calcium and excessive cell proliferation. Our results found that two CaMK proteins, CaMKIV and CaMKII δ, cause increased proliferation and are found at higher concentrations in patients with IPAH. We found that these two CamK proteins are necessary for the increased activity of AKT and PDGFR, two proteins involved in the proliferation pathway. While more research is needed, these results suggest that CaMKIV and CaMKII δ could be targets for the treatment of hypertension.