Basal Blood Pressure Characterization of Smooth Muscle Specific IL-36R FLox Knockout Mice

Background and Objectives: Hypertension is a detrimental factor in premature death worldwide, the underlying mechanism remain largely unknown, and the current treatments are moderate.  Preliminary studies showed an association of hypertension with an increased expression of interleukin 36 receptor (IL-36R), an inflammatory regulator, in aortic vascular smooth muscle cells (VSMCs), leading to a hypothesis that reducing IL-36R prevents the pathogenesis of hypertension. To determine the role of IL-36R during the development of hypertension in response to pathological stimulation, we developed genetic IL-36R knock out (KO) mice and  characterized the blood pressure in these mice at the basal level without detrimental stimulations. Methods and Results: To develop a VSMC-specific  KO mice, we designed and generated IL-36R Flox mice and cross-mated these mice with SM22 Cre^+/- transgenic mice; the genotypes of the offspring were identified by PCR with the DNA extract from mouse tail tissues.  Non-invasive tail cuff blood pressure was performed on age and sex matched IL-36R heterozygous KO mice (IL-36R Flox^+/-/SM22 Cre^+/-) and their genetic control mouse lines, including IL-36R Flox^+/-, SM22 Cre^+/- and wild type (WT) mice. There was no significant difference in measured systolic and diastolic blood pressure (SBP and DBP) as well as the calculated mean blood pressure (MAP) between IL-36R heterozygous KO mice and the control mice lines at 3 months of age. Conclusion: The data reveal that partial reduction of IL-36R in vascular smooth muscle cells does not alter SBP, DBP, or MAP at baseline.  In the future we intend to analyze the effects of knocking out vascular IL-36R in an Angiotensin II-induced hypertension mouse model to validate whether IL-36R mediates hypertension under pathological conditions.