Abstract: SA-PO763
Revealing Novel Signaling Pathways Affected in Glomeruli During Salt-Sensitive Hypertension
Session Information
- Hypertension and CVD: Mechanisms
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1503 Hypertension and CVD: Mechanisms
Authors
- Anwar, Fabiha, Augusta University, Augusta, Georgia, United States
- Lysikova, Daria, Augusta University, Augusta, Georgia, United States
- Schibalski, Ryan, Augusta University, Augusta, Georgia, United States
- Domondon, Mark, Medical University of South Carolina, Charleston, South Carolina, United States
- Shamatova, Margarita, Augusta University, Augusta, Georgia, United States
- Stadler, Krisztian, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
- Spires, Denisha R., Augusta University, Augusta, Georgia, United States
- Ilatovskaya, Daria, Augusta University, Augusta, Georgia, United States
Background
Salt-sensitive hypertension (SS-HTN) is defined by an increase in blood pressure resulting from an elevated salt intake; it is characterized by the development of hypertensive glomerulosclerosis. There is a gap in knowledge regarding factors that might contribute to glomerular damage in SS-HTN. The goal of this study was to assess the transcriptomic changes that accompany glomerulosclerosis in SS-HTN.
Methods
8-week-old Dahl Salt Sensitive rats were fed a normal (0.4% NaCl, NS) or high salt diet (4% NaCl, HS, to induce hypertension) for 3 weeks. At the endpoint, glomeruli were obtained from the cortex using differential sieving. Total mRNA was isolated from the glomeruli and subjected to NextGen sequencing; transcriptomic data was analyzed using IPA software. The cutoff value for the experimental fold-change (EFC) was 1.5; p value < 0.05 was considered significant.
Results
149 genes were found to be differentially expressed in glomeruli from HS and NS diet fed rats (107 and 42 were down- and up-regulated). We recorded changes in several signaling pathways: GPCR signaling was suppressed, including leptin/melanocortin, AMPK/mTOR, and ERK/MAPK pathways (Elf3 (EFC 1.8); Mc4r (-5.0), Gator2 (-4.3), Azgp1 (-3.6), Lepr (-2.9), Nr4a1 (-2.4), Pki (-2.5), Rgs2 (-1.8)). We report changes in calcium regulation (Calb (1.6), Cav2.1 (-3.6), Prkce (-3.0), Carf (-2.2), Ip3kb (-1.8)), cellular metabolism (Ltc4s (2.3), Apobec1 (1.5), Sdr42e1 (1.5), Acaca (-3.2), Fads3 (-2.6), Sdhaf3 (-2.3), Ren (-1.9), Cox14 (-1.7), Cyp4f2 (-1.6), Mgll (-1.6) Cyp2d22 (-1.5), Ch25h (-1.5), Gnpda2 (-1.5)), immune response, apoptosis, and inflammation (Mrc1 (1.5), NFkB (-2.8), Xiap (-2.8), Fcgr2a (-2.7), Marco (-2), Hla-a (-1.7)), as well as fibrosis and cell proliferation (Myl3 (1.7), Ccnd2 (1.5), Fmnl3 (-3.5), c-Rel (-2.8), Cdk13 (-1.8), Cdkn1b (-1.6), Wnt5a (-1.6)), and solute transporters (Slc14a1 (2.8), Slco1a1 (-2.2), Slc2a10 (-1.7), Slc38a3 (-1.7), Slc6a6 (-1.6), Slc38a6 (-1.5)).
Conclusion
We revealed here novel gene networks affected in glomeruli during SS-HTN. Alignment of this data with other existing ‘omics analyses is necessary to provide further insight into the development of hypertensive glomerulosclerosis.
Funding
- Other NIH Support