Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
2017
Hypertension is a well-established risk
factor for adverse cardiovascular events
and older age is a risk factor for the
development of hypertension. Genome
wide 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 was observed in small
mesenteric arteries from animals 9
months of age and older, indicative of
eutrophic remodeling. 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.
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