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Blockade of Trpm7 in the Carotid Body area reversed Obesity‐Induced Hypertension
Author(s) -
Shin MiKyung,
Gu Chenjuan,
Kim Lenise,
Yeung Bonnie,
Lee Rachel,
Pham Luu,
Tang WanYee,
Sham James,
Polotsky Vsevolod
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03551
Subject(s) - leptin , trpm7 , medicine , endocrinology , blood pressure , small hairpin rna , gene knockdown , obesity , chemistry , receptor , ion channel , gene , biochemistry
Rationale Obesity leads to cardiovascular morbidity and mortality acting via multiple mechanisms including hypertension. One of the mechanisms of obesity‐induced hypertension is an adipocyte‐produced hormone leptin, which activates the sympathetic nervous system. We have recently reported that acute leptin infusion induces hypertension acting via the TRPM7 cation channel in the carotid bodies (CB). Here, we examined the relevance of TRPM7 signaling in CB for the pathogenesis of hypertension in diet‐induced obesity (DIO) with high circulating leptin levels. We hypothesize that DIO causes hypertension acting on CB TRPM7. Methods DIO male mice (n =11) were implanted with telemetry in the left femoral artery for continuous blood pressure monitoring. Trpm7 was silenced in the carotid body areas by transfection with Ad‐Trpm7 shRNA (n = 6); control mice (N = 5) were transfected with Ad‐CON‐shRNA . Plasma leptin level were measured by ELISA before and after tranfection; RT‐PCR was performed to confirm Trpm7 knockdown. Result Trpm7 shRNA group induced a decrease in Trpm7 mRNA expression in the CB compared to control (0.089±0.02 vs 0.416±0.08 relatively to a house‐keeping gene Rpl19 respectively, p<0.01 ). In Trpm7 shRNA treated group, blood pressure decreased from 119.0±2.2 mmHg to 109.6±1.4 mmHg ( p<0.01 ), whereas scrambled shRNA had no effect (from 114.8±0.9 mmHg to 116.3±2.6 mmHg) (Fig. 1). Both groups had similar levels of plasma leptin at baseline, which did not change after transfection. Conclusion Our study has shown that downregulation of Trpm7 in carotid bodies abolished hypertension in obese mice.