Roles of Vascular Risk Factors In A Neurological Disease

Abstract

AimWe have previously reported that angioneurins such as vascular endothelial growth factor that exert both vasculotrophic and neurotrophic activities can play a diverse role and transform into a pathogenic mediator of post‐hemorrhagic hydrocephalus in young brains. The objective of this study was to better understand the roles of vascular risk factors in the brain with an age‐related neurological condition.MethodsLiteratures reporting a relationship between vascular risk factors such as arterial stiffness and age‐related disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) were surveyed. Elastin gene expression was quantified in the thoracic aorta of male mice with young and old age and of young mice fed with high fat high sucrose (HFHS) diet. Aortic stiffness was assessed in vivo using ultrasound and compared to age‐, diet‐, and gender‐matched mice with constitutive deletion of phospholipase A2 group 6 (PLA2g6). Gene expression analysis was conducted on aortic medial layer RNA and validated by elastic fiber staining. Cell‐specific effect on elastin gene expression and arterial stiffness was further tested in a mouse model with SMC‐specific impairment of PLA2g6.ResultsAn inverse interrelationship between the PD and vascular risk factors including smoking and vascular stiffness were noted. Animal experiments revealed that aging and HFHS‐diet induced arterial stiffening in wild type (WT) animals but not in PLA2g6 knockout mice. The qRT‐PCR revealed that elastin gene expression was significantly elevated regardless of age in PLA2g6 impaired mice. The mRNA expression of Sp1 transcription factor was significantly increased in aged PLA2g6 knockout aorta. Mice with SMC‐specific deletion of PLA2g6 at young age showed significantly reduced arterial stiffness with elevated elastin during HFHS diet.ConclusionThese results demonstrate that a vascular risk factor such as arterial stiffness declines with aging through modulation of age‐induced loss of elastin in arteries of mice with impaired PLA2g6 exhibiting PD symptoms. Molecular targets promoting expressions of vasculoprotective gene such as elastin along the cell‐specific pathway may provide novel therapies for the protection against an increase of vascular risk and the better understanding to the associated age‐related neurodegeneration.Support or Funding InformationJ.W.S is supported by the Fellowship from the Multidisciplinary Postdoctoral Training Program in Cardiovascular Research (NIH 5T32HL007224‐39).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.