Abstract
SummaryHypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension. Here, we present the effects of reduction in the expression of PMCA1 on BP and small artery structure and function when combined with advancing age. Heterozygous PMCA1 null mice (PMCA1Ht) were generated and conscious BP was measured at 6 to 18 months of age. Passive and active properties of isolated small mesenteric arteries were examined by pressure myography. PMCA1Ht mice exhibited normal BP at 6 and 9 months of age but developed significantly elevated BP when compared to age‐matched wild‐type controls at ≥12 months of age. Decreased lumen diameter, increased wall thickness and increased wall:lumen ratio were observed in small mesenteric arteries from animals 9 months of age and older, indicative of eutrophic remodelling. Increases in mesenteric artery intrinsic tone and global intracellular calcium were evident in animals at both 6 and 18 months of age. Thus, decreased expression of PMCA1 is associated with increased BP when combined with advancing age. Changes in arterial structure precede the elevation of BP. Pathways involving PMCA1 may be a novel target for BP regulation in the elderly.
Highlights
Cardiovascular diseases are the world’s leading cause of morbidity and mortality
Immunoblot analysis of tissues from 6-month-old animals showed that plasma membrane calcium ATPase 1 (PMCA1) protein expression was reduced by 45–55% in the aorta, heart, brain and kidney of PMCA1Ht mice compared to WT controls (Fig. 1A)
Reduced expression of PMCA1 had no significant effect on the mRNA level of Atp2b4 in aorta from 6 months (P = 0.672) or 18-month-old (P = 0.503) animals, the relative Atp2b4 mRNA level was found to be significantly reduced with age (Fig. 1C)
Summary
Hypertension is a major modifiable risk factor for adverse cardiovascular events including stroke and aneurysm, and for heart and renal failure (Kearney et al, 2005). Around 90% of people with hypertension suffer from essential, known as primary, hypertension (Mancia et al, 2013), for which there is no single or clearly identifiable cause. The prevalence of essential hypertension increases with age, in a roughly linear relationship (Buford, 2016), with around 60% of people over 70 years of age being hypertensive (Buford, 2016). It is ever more important to understand the underlying basis of BP control and the factors which may increase the risk of developing hypertension with aging
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