Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries.

Abstract

Hypertension 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.

• Authors: Robert Little, Min Zi, Sally K Hammad, Loan Nguyen, Alexandra Njegic, Sathishkumar Kurusamy, Sukhpal Prehar, Angel L Armesilla, Ludwig Neyses, Clare Austin, Elizabeth J Cartwright
• Journal: Aging cell (Aging Cell) Vol. 16 Issue 5 Pg. 1104-1113 (10 2017) ISSN: 1474-9726 [Electronic] England
• PMID: 28795531 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Chemical References

• Plasma Membrane Calcium-Transporting ATPases
• Atp2b1 protein, mouse
• Calcium

Topics

• Aging (genetics, metabolism)
• Animals
• Blood Pressure (physiology)
• Calcium (metabolism)
• Gene Expression
• Heterozygote
• Hypertension (genetics, metabolism, physiopathology)
• Male
• Mesenteric Arteries (metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myography
• Plasma Membrane Calcium-Transporting ATPases (deficiency, genetics)
• Vascular Remodeling (genetics)
• Vascular Resistance (genetics)