Key result
NLRP3/ASC knockout or anti-IL1β therapy protects mice from renovascular hypertension and lowers circulating renin.
Why the study?
The contribution of the Nlrp3-inflammasome to hypertension is not established despite its known role in other inflammatory diseases.
Does Nlrp3-inflammasome deficiency or IL1β inhibition prevent the development of renovascular hypertension in a mouse model?
Does Nlrp3-inflammasome deficiency or IL1β inhibition prevent the development of renovascular hypertension in a mouse model?
The Nlrp3-inflammasome and IL1β mediate the development of renin-dependent renovascular hypertension in mice, identifying a potential novel therapeutic target.
Nlrp3/IL-1β inhibition may attenuate experimental renovascular hypertension; leaves open translation to human disease.
Objective: Recent studies have implicated an enhanced secretion of IL1β through activation of the Nod-like receptor family, pyrin domain containing 3 (Nlrp3)-inflammasome as the pro-inflammatory signal in animal models of the gout, chronic kidney disease (CKD), atherosclerosis, metabolic syndrome, type 2 diabetes mellitus, but its contribution to hypertension is not established. We aimed to demonstrate the role of the Nlrp3-inflammasome in the two-kidneys, one clip (2K1C) Goldblatt model of hypertension in Nlrp3-/- and apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc)-/- and wild type control male mice. Study design: 2K1C hypertension was generated by narrowing left renal artery using U-shaped stainless steel clip. BP and heart rate were recorded intra-arterially with a computerized data-acquisition system in conscious mice. Plasma renin activity and concentration were measured by radioimmunoassay. Renal transcript levels of Nlrp3, Asc, Casp1, IL1A, IL1β, and IL6 were assessed by RT-Q-PCR. Results: Results show that Nlrp3-/- and Asc-/- mice are protected from developing hypertension and have lower circulating levels of plasma renin and serum amyloid A (SAA) and IL6, in comparison to wild type (WT) control mice. RNA levels of SAA, Nlrp3, and IL1β are increased in the ischemic kidney of the WT control mice. Administration of anti-IL1β antibody to the WT control mice attenuated the increase of blood pressure and renin in the 2K1C model. The results suggest that NALP3 inflammasome has an impact on blood pressure and renin secretion during renal hypoperfusion induced by renal arterial clip and contributes to renin-dependent renovascular hypertension. Conclusion: These findings show that Nlrp3-inflammasome mediated production of IL1 is linked to the development of renovascular hypertension and might be a novel target for the treatment of renovascular hypertension, CKD and other inflammatory diseases with hypertension.
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AQing Wang Alexander So (2013) studied Renovascular hypertension. Nlrp3 and Asc gene knockout / anti-IL1β antibody vs. Wild type control mice was evaluated on Development of hypertension and circulating levels of plasma renin. Nlrp3-/- and Asc-/- mice, and wild type mice treated with anti-IL1β antibody, were protected from developing 2K1C renovascular hypertension and had lower circulating renin levels.
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