Deletion of JNK2 prevents vitamin-D-deficiency-induced hypertension and atherosclerosis in mice

Jisu Oh, Amy E. Riek, Rong M. Zhang, Samantha A.S. Williams, Isra Darwech, Carlos Bernal-Mizrachi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The c-Jun N-terminal kinase 2 (JNK2) signaling pathway contributes to inflammation and plays a key role in the development of obesity-induced insulin resistance and cardiovascular disease. Macrophages are key cells implicated in these metabolic abnormalities. Active vitamin D downregulates macrophage JNK activation, suppressing oxidized LDL cholesterol uptake and foam cell formation and promoting an anti-inflammatory phenotype. To determine whether deletion of JNK2 prevents high blood pressure and atherosclerosis known to be induced by vitamin D deficiency in mice, we generated mice with knockout of JNK2 in a background susceptible to diet-induced atherosclerosis (LDLR −/− ). JNK2 −/− LDLR −/− and LDLR −/− control mice were fed vitamin D-deficient chow for 8 weeks followed by vitamin D-deficient high fat diet (HFD) for 10 weeks and assessed before and after HFD. There was no difference in fasting glucose, cholesterol, triglycerides, or free fatty acid levels. However, JNK2 −/− mice, despite vitamin D-deficient diet, had 20–30 mmHg lower systolic (SBP) and diastolic (DBP) blood pressure before HFD compared to control mice fed vitamin D-deficient diets, with persistent SBP differences after HFD. Moreover, deletion of JNK2 reduced HFD-induced atherosclerosis by 30% in the proximal aorta when compared to control mice fed vitamin D-deficient diets. We have previously shown that peritoneal macrophages obtained from LDLR −/− mice fed vitamin D-deficient HFD diets have higher foam cell formation compared to those from mice on vitamin D-sufficient HFD. The increased total cellular cholesterol and modified cholesterol uptake in macrophages from mice on vitamin D-deficient HFD were blunted by deletion of JNK2. These data suggest that JNK2 signaling activation is necessary for the atherosclerosis and hypertension induced by vitamin D deficiency.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
StatePublished - Mar 2018


  • Atherosclerosis
  • Hypertension
  • JNK
  • Macrophages
  • Vitamin D


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