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Male-associated hypertension in LDL-R deficient mice
1Department of Cardiovascular Biology and Molecular Epidemiology Program, Wayne Hughes Institute, 2665 Long Lake Road, St. Paul, Minnesota, 55113, USA.
Insights
Lipoprotein (a) did not cause hypertension in mice. However, low-density lipoprotein receptor (LDL-R) deficiency was linked to hypertension in males, suggesting a role in vascular tone regulation.
Area of Science:
- Cardiovascular Science
- Genetics
- Hypertension Research
Background:
- Hypertension prevalence differs between ethnic groups, with higher rates in African Americans.
- Lipoprotein (a) [Lp(a)] levels are elevated in African Americans and are an independent cardiovascular disease risk factor.
- The genetic basis for hypertension disparities and the role of Lp(a) remain unclear.
Purpose of the Study:
- To investigate the potential link between Lp(a) and hypertension.
- To explore the role of low-density lipoprotein receptor (LDL-R) deficiency in hypertension and stroke susceptibility.
Main Methods:
- Assessed blood pressure in transgenic mice expressing apolipoprotein(a).
- Evaluated blood pressure in apoE deficient, LDL-R deficient, and wild type mice.
- Determined sensitivity to photochemically induced cerebral stroke in LDL-R deficient mice.
Main Results:
- Apolipoprotein(a) expression did not correlate with hypertension in the studied mice.
- LDL-R deficient mice unexpectedly developed male-associated hypertension.
- LDL-R deficient mice showed increased sensitivity to cerebral stroke, with a modest sexual dimorphism.
Conclusions:
- LDL-R deficiency, not Lp(a) expression, is associated with hypertension in mice.
- This finding may explain increased atherosclerosis in male LDL-R deficient mice and familial hypercholesterolemia patients.
- LDL-R deficiency appears to induce previously unrecognized alterations in vascular tone.
Abstract:
Hypertension is more common among African Americans than Americans of European descent. However, the genetic etiology has not been defined. Similarly, lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is higher among African Americans. To explore the relationship between Lp (a) and hypertension, we measured the blood pressure of transgenic mice expressing apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we also determined blood pressure for apoE deficient mice, low density lipoprotein-receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression was not associated with hypertension. Surprisingly, LDL-R deficient mice exhibited male-associated hypertension. This observation could explain the higher incidence of atherosclerosis in male LDL-R deficient mice and human familial hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to photochemically induced cerebral stroke. However, this hypersensitivity was only modestly associated with sexual dimorphism. The presented data suggest that LDL-R deficiency results in hitherto unrecognized changes in the vascular tone.