Resistance artery creatine kinase mRNA and blood pressure in humans
Fares A Karamat1, Inge Oudman, Carrie Ris-Stalpers
1Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Room F4-253, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. F.A.Karamat@amc.uva.nl.
Insights
Creatine kinase B mRNA levels in human resistance arteries are strongly linked to blood pressure. Hypertensive individuals showed nearly double the mRNA levels compared to normotensive individuals, suggesting a vascular role.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Hypertension Research
Background:
- Hypertension is a primary risk factor for cardiovascular mortality.
- Circulating creatine kinase is a known predictor of blood pressure.
- Creatine kinase-BB's role in vascular contractility via ATP regeneration is hypothesized.
Purpose of the Study:
- To investigate the association between creatine kinase isoenzyme mRNA levels in human resistance arteries and blood pressure.
- To determine if creatine kinase B mRNA expression correlates with systolic and diastolic blood pressure.
Main Methods:
- Resistance arteries were isolated from omental fat tissue of women.
- Blood pressure was measured in a sitting position.
- Quantitative real-time polymerase chain reaction (qPCR) was used to assess arteriolar creatine kinase isoenzyme mRNA levels.
Main Results:
- A near-perfect correlation was observed between creatine kinase B mRNA copy numbers and diastolic blood pressure (r=0.9).
- Creatine kinase B mRNA levels were also well correlated with systolic blood pressure.
- Hypertensive individuals exhibited a 90% relative increase in resistance artery creatine kinase B mRNA compared to normotensive individuals (19.3 vs. 10.1, P=0.0045).
Conclusions:
- This study provides the first direct evidence linking resistance artery creatine kinase mRNA expression to blood pressure levels.
- Creatine kinase B mRNA levels nearly double in hypertensive individuals, suggesting its involvement in vascular pressor responses.
- These findings support a potential role for creatine kinase in the pathophysiology of hypertension.
Abstract:
Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6-1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature's pressor responses.
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