Key Points
- To determine whether targeted conditional overexpression of rat vascular chymase in smooth muscle cells is sufficient to cause hypertension and vascular structural changes.
- Engineered transgenic mice with smooth muscle cell-targeted conditional expression of rat vascular chymase (RVCH) regulated by the tetracycline-controlled transactivator (tTA) and repressed by dietary doxycycline.
- Assessed blood pressure via carotid artery cannulation at 10-12 weeks of age, arterial wall remodeling through PCNA immunoreactivity, and vascular function using mesenteric artery perfusion myography.
- Systolic blood pressure was significantly elevated in tTA+/RVCH+ mice compared to nonbinary transgenic controls (136 ± 4 vs. 109 ± 3 mmHg, P < 0.05), alongside higher diastolic and mean pressures, all of which were reversed by doxycycline.
- Mesenteric arteries from tTA+/RVCH+ mice showed increased medial thickening (0.82 ± 0.1 vs. 0.42 ± 0.02, P < 0.05) linked to smooth muscle cell proliferation, which was prevented by doxycycline.
- Perfusion myography demonstrated increased phenylephrine-induced vasoconstriction and impaired methacholine-induced vasodilation in tTA+/RVCH+ vessels compared with control and doxycycline-treated groups.
Structured PICO
Does targeted overexpression of vascular chymase cause hypertension in transgenic mice?
PPopulationTransgenic mice with targeted conditional expression of rat vascular chymase (RVCH) to smooth muscle cells (SMCs)
IInterventionConditional overexpression of RVCH (tTA+/RVCH+ mice)
CComparatorNonbinary transgenic littermates and doxycycline-treated group (which reverses expression)
OOutcomeSystolic blood pressure at 10-12 weeks of agesurrogate
Targeted overexpression of vascular chymase in smooth muscle cells is sufficient to cause hypertensive arteriopathy in mice, identifying it as a potential therapeutic target.