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Article: Editorial: Renal Function in Acute and Chronic Kidney Diseases.

Imig, John D / Hye Khan, Md Abdul / Zhao, Xueying

2020 Volume 11, Page(s) 625353

Language	English
Publishing date	2020-12-03
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2020.625353
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Article ; Online: Dual soluble epoxide hydrolase inhibitor - farnesoid X receptor agonist interventional treatment attenuates renal inflammation and fibrosis.

Khan, Md Abdul Hye / Nolan, Benjamin / Stavniichuk, Anna / Merk, Daniel / Imig, John D

Frontiers in immunology

2024 Volume 14, Page(s) 1269261

Abstract: Introduction: Renal fibrosis associated with inflammation is a critical pathophysiological event in chronic kidney disease (CKD). We have developed DM509 which acts concurrently as a farnesoid X receptor agonist and a soluble epoxide hydrolase inhibitor ...

Abstract	Introduction: Renal fibrosis associated with inflammation is a critical pathophysiological event in chronic kidney disease (CKD). We have developed DM509 which acts concurrently as a farnesoid X receptor agonist and a soluble epoxide hydrolase inhibitor and investigated DM509 efficacy as an interventional treatment using the unilateral ureteral obstruction (UUO) mouse model. Methods: Male mice went through either UUO or sham surgery. Interventional DM509 treatment (10mg/kg/d) was started three days after UUO induction and continued for 7 days. Plasma and kidney tissue were collected at the end of the experimental protocol. Results: UUO mice demonstrated marked renal fibrosis with higher kidney hydroxyproline content and collagen positive area. Interventional DM509 treatment reduced hydroxyproline content by 41% and collagen positive area by 65%. Renal inflammation was evident in UUO mice with elevated MCP-1, CD45-positive immune cell positive infiltration, and profibrotic inflammatory gene expression. DM509 treatment reduced renal inflammation in UUO mice. Renal fibrosis in UUO was associated with epithelial-to-mesenchymal transition (EMT) and DM509 treatment reduced EMT. UUO mice also had tubular epithelial barrier injury with increased renal KIM-1, NGAL expression. DM509 reduced tubular injury markers by 25-50% and maintained tubular epithelial integrity in UUO mice. Vascular inflammation was evident in UUO mice with 9 to 20-fold higher ICAM and VCAM gene expression which was reduced by 40-50% with DM509 treatment. Peritubular vascular density was reduced by 35% in UUO mice and DM509 prevented vascular loss. Discussion: Interventional treatment with DM509 reduced renal fibrosis and inflammation in UUO mice demonstrating that DM509 is a promising drug that combats renal epithelial and vascular pathological events associated with progression of CKD.
MeSH term(s)	Male ; Mice ; Animals ; Epoxide Hydrolases ; Hydroxyproline ; Nephritis/drug therapy ; Nephritis/complications ; Ureteral Obstruction/complications ; Ureteral Obstruction/pathology ; Renal Insufficiency, Chronic/etiology ; Renal Insufficiency, Chronic/complications ; Inflammation/pathology ; Collagen/metabolism ; Fibrosis
Chemical Substances	Epoxide Hydrolases (EC 3.3.2.-) ; Hydroxyproline (RMB44WO89X) ; Collagen (9007-34-5)
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1269261
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Article ; Online: Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences.

Goorani, Samaneh / Khan, Abdul Hye / Mishra, Abhishek / El-Meanawy, Ashraf / Imig, John D

Kidney & blood pressure research

2024 Volume 49, Issue 1, Page(s) 69–80

Abstract: Introduction: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a ... ...

Abstract	Introduction: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a greater prevalence of end-stage renal disease. In addition, low birth weight and low nephron number are associated with increased risk for CKD. This study examined the development and severity of unilateral ureter obstruction (UUO)-induced renal fibrosis in male and female wild-type (ROP +/+) and mutant (ROP Os/+) mice, a mouse model of low nephron number. Methods: Male and female ROP +/+ and ROP Os/+ mice were subjected to UUO, and kidney tissue was collected at the end of the 10-day experimental period. Kidney histological analysis and mRNA expression determined renal fibrosis, tubular injury, collagen deposition, extracellular matrix proteins, and immune cell infiltration. Results: Male and female UUO mice demonstrated marked renal injury, kidney fibrosis, and renal extracellular matrix production. Renal fibrosis and α-smooth muscle actin were increased to a similar degree in ROP +/+ and ROP Os/+ mice with UUO of either sex. There were also no sex differences in renal tubular cast formation or renal infiltration of macrophage in ROP +/+ and ROP Os/+ UUO mice. Interestingly, renal fibrosis and α-smooth muscle actin were 1.5-3-fold greater in UUO-ROP +/+ compared to UUO-ROP Os/+ mice. Renal inflammation phenotypes following UUO were also 30-45% greater in ROP +/+ compared to ROP Os/+ mice. Likewise, expression of extracellular matrix and renal fibrotic genes was greater in UUO-ROP +/+ mice compared to UUO-ROP Os/+ mice. In contrast to these findings, ROP Os/+ mice with UUO demonstrated glomerular hypertrophy with 50% greater glomerular tuft area compared to ROP +/+ with UUO. Glomerular hypertrophy was not sex-dependent in any of the genotypes of ROP mice. These findings provide evidence that low nephron number contributes to UUO-induced glomerular hypertrophy in ROP Os/+ mice but does not enhance renal fibrosis, inflammation, and renal tubular injury. Conclusion: Taken together, we demonstrate that low nephron number contributes to enhanced glomerular hypertrophy but not kidney fibrosis and tubular injury. We also demonstrate that none of the changes caused by UUO was affected by sex in any of the ROP mice genotypes.
MeSH term(s)	Female ; Male ; Animals ; Mice ; Ureteral Obstruction/complications ; Ureteral Obstruction/metabolism ; Actins/metabolism ; Sex Characteristics ; Kidney/pathology ; Renal Insufficiency, Chronic/complications ; Inflammation/pathology ; Fibrosis ; Hypertrophy/pathology ; Mice, Inbred C57BL ; Disease Models, Animal
Chemical Substances	Actins
Language	English
Publishing date	2024-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1326018-2
ISSN	1423-0143 ; 1420-4096
ISSN (online)	1423-0143
ISSN	1420-4096
DOI	10.1159/000535809
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Article ; Online: Salt-sensitive hypertension after reversal of unilateral ureteral obstruction.

Imig, John D / Khan, Md Abdul Hye / Stavniichuk, Anna / Jankiewicz, Wojciech K / Goorani, Samaneh / Yeboah, Michael M / El-Meanawy, Ashraf

Biochemical pharmacology

2023 Volume 210, Page(s) 115438

Abstract: The incidence of ureter obstruction is increasing and patients recovering from this kidney injury often progress to chronic kidney injury. There is evidence that a long-term consequence of recovery from ureter obstruction is an increased risk for salt- ... ...

Abstract	The incidence of ureter obstruction is increasing and patients recovering from this kidney injury often progress to chronic kidney injury. There is evidence that a long-term consequence of recovery from ureter obstruction is an increased risk for salt-sensitive hypertension. A reversal unilateral ureteral obstruction (RUUO) model was used to study long-term kidney injury and salt-sensitive hypertension. In this model, we removed the ureteral obstruction at day 10 in mice. Mice were divided into four groups: (1) normal salt diet, (2) high salt diet, (3) RUUO normal salt diet, and (4) RUUO high salt diet. At day 10, the mice were fed a normal or high salt diet for 4 weeks. Blood pressure was measured, and urine and kidney tissue collected. There was a progressive increase in blood pressure in the RUUO high salt diet group. RUUO high salt group had decreased sodium excretion and glomerular injury. Renal epithelial cell injury was evident in RUUO normal and high salt mice as assessed by neutrophil gelatinase-associated lipocalin (NGAL). Kidney inflammation in the RUUO high salt group involved an increase in F4/80 positive macrophages; however, CD3+ positive T cells were not changed. Importantly, RUUO normal and high salt mice had decreased vascular density. RUUO was also associated with renal fibrosis that was further elevated in RUUO mice fed a high salt diet. Overall, these findings demonstrate long-term renal tubular injury, inflammation, decreased vascular density, and renal fibrosis following reversal of unilateral ureter obstruction that could contribute to impaired sodium excretion and salt-sensitive hypertension.
MeSH term(s)	Mice ; Animals ; Ureteral Obstruction/complications ; Ureteral Obstruction/pathology ; Kidney/pathology ; Hypertension/complications ; Sodium Chloride, Dietary/adverse effects ; Sodium ; Fibrosis
Chemical Substances	Sodium Chloride, Dietary ; Sodium (9NEZ333N27)
Language	English
Publishing date	2023-01-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2023.115438
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Article: Epoxyeicosatrienoic Acid Analog EET-A Blunts Development of Lupus Nephritis in Mice.

Hye Khan, Md Abdul / Stavniichuk, Anna / Sattar, Mohammad Abdul / Falck, John R / Imig, John D

Frontiers in pharmacology

2019 Volume 10, Page(s) 512

Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that causes life threatening renal disease and current therapies are limited with serious side-effects. CYP epoxygenase metabolites of arachidonic acid epoxyeicosatrienoic ... ...

Abstract	Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that causes life threatening renal disease and current therapies are limited with serious side-effects. CYP epoxygenase metabolites of arachidonic acid epoxyeicosatrienoic acids (EETs) demonstrate strong anti-inflammatory and kidney protective actions. We investigated the ability of an orally active EET analog, EET-A to prevent kidney injury in a mouse SLE model. Twenty-weeks old female NZBWF1 (SLE) and age-matched NZW/LacJ (Non SLE) were treated with vehicle or EET-A (10 mg/kg/d, p.o.) for 14 weeks and urine and kidney tissues were collected at the end of the protocol. SLE mice demonstrated marked renal chemotaxis with 30-60% higher renal mRNA expression of CXC chemokine receptors (CXCR) and CXC chemokines (CXCL) compared to Non SLE mice. In SLE mice, the elevated chemotaxis is associated with 5-15-fold increase in cytokine mRNA expression and elevated inflammatory cell infiltration in the kidney. SLE mice also had elevated BUN, serum creatinine, proteinuria, and renal fibrosis. Interestingly, EET-A treatment markedly diminished renal CXCR and CXCL renal mRNA expression in SLE mice. EET-A treatment also reduced renal TNF-α, IL-6, IL-1β, and IFN-γ mRNA expression by 70-80% in SLE mice. Along with reductions in renal chemokine and cytokine mRNA expression, EET-A reduced renal immune cell infiltration, BUN, serum creatinine, proteinuria and renal fibrosis in SLE mice. Overall, we demonstrate that an orally active EET analog, EET-A prevents renal injury in a mouse model of SLE by reducing inflammation.
Language	English
Publishing date	2019-05-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2019.00512
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Article ; Online: Kidney-Targeted Epoxyeicosatrienoic Acid Analog, EET-F01, Reduces Inflammation, Oxidative Stress, and Cisplatin-Induced Nephrotoxicity.

Imig, John D / Hye Khan, Md Abdul / Burkhan, Anna / Chen, Guan / Adebesin, Adeniyi Michael / Falck, John R

International journal of molecular sciences

2021 Volume 22, Issue 6

Abstract: Although epoxyeicosatrienoic acid (EET) analogs have performed well in several acute and chronic kidney disease models, targeted delivery of EET analogs to the kidney can be reasonably expected to reduce the level of drug needed to achieve a therapeutic ... ...

Abstract	Although epoxyeicosatrienoic acid (EET) analogs have performed well in several acute and chronic kidney disease models, targeted delivery of EET analogs to the kidney can be reasonably expected to reduce the level of drug needed to achieve a therapeutic effect and obviate possible side effects. For EET analog kidney-targeted delivery, we conjugated a stable EET analog to folic acid via a PEG-diamine linker. Next, we compared the kidney targeted EET analog, EET-F01, to a well-studied EET analog, EET-A. EET-A or EET-F01 was infused i.v. and plasma and kidney tissue collected. EET-A was detected in the plasma but was undetectable in the kidney. On the other hand, EET-F01 was detected in the plasma and kidney. Experiments were conducted to compare the efficacy of EET-F01 and EET-A for decreasing cisplatin nephrotoxicity. Cisplatin was administered to WKY rats treated with vehicle, EET-A (10 mg/kg i.p.) or EET-F01 (20 mg/kg or 2 mg/kg i.p.). Cisplatin increased kidney injury markers, viz., blood urea nitrogen (BUN), N-acetyl-β-(D)-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), and thiobarbituric acid reactive substances (TBARS). EET-F01 was as effective as EET-A in decreasing BUN, NAG, KIM-1, TBARS, and renal histological injury caused by cisplatin. Despite its almost 2×-greater molecular weight compared with EET-A, EET-F01 was comparably effective in decreasing renal injury at a 10-fold
MeSH term(s)	8,11,14-Eicosatrienoic Acid/analogs & derivatives ; 8,11,14-Eicosatrienoic Acid/chemistry ; 8,11,14-Eicosatrienoic Acid/pharmacokinetics ; 8,11,14-Eicosatrienoic Acid/pharmacology ; Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cisplatin ; Female ; Humans ; Inflammation/metabolism ; Inflammation/prevention & control ; Kidney/metabolism ; Kidney/pathology ; Kidney Diseases/chemically induced ; Kidney Diseases/metabolism ; Kidney Diseases/prevention & control ; Male ; Mice, Nude ; Oxidative Stress/drug effects ; Rats, Inbred WKY ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays/methods ; Mice ; Rats
Chemical Substances	11,12-epoxy-5,8,14-eicosatrienoic acid (5DOQ38R4UW) ; 8,11,14-Eicosatrienoic Acid (FC398RK06S) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2021-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22062793
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Article ; Online: A dual farnesoid X receptor/soluble epoxide hydrolase modulator treats non-alcoholic steatohepatitis in mice.

Hye Khan, Md Abdul / Schmidt, Jurema / Stavniichuk, Anna / Imig, John D / Merk, Daniel

Biochemical pharmacology

2019 Volume 166, Page(s) 212–221

Abstract: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the most prevalent metabolic liver disorders and a serious global health burden. NAFLD/NASH pathogenesis and progression are highly multi-factorial and likely demand a ...

Abstract	Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the most prevalent metabolic liver disorders and a serious global health burden. NAFLD/NASH pathogenesis and progression are highly multi-factorial and likely demand a combination of multiple mechanisms to provide a more effective treatment. We have developed a dual farnesoid X receptor agonist (FXRA)/soluble epoxide hydrolase inhibitor (sEHi) to simultaneously address two validated and complementary modes of action in NASH treatment. Here we report the in vivo profiling for this FXRA/sEHi in toxin- and diet-induced rodent NASH models. In streptozotocin-induced NASH as a proof-of-concept study, the experimental FXRA/sEHi drug robustly prevented hepatic steatosis and fibrosis, and improved lipid homeostasis as well as biochemical markers of liver health. In methionine-choline-deficient high-fat diet-induced NASH, FXRA/sEHi treatment reduced hepatic steatosis and fibrosis to levels similar to healthy animals and demonstrated anti-inflammatory activity confirming that dual FXRA/sEHi modulation produces a triad of complementary anti-NASH effects. Our results validate dual FXRA/sEHi modulation as an effective therapeutic strategy to treat NASH and advocates for a combinational drug therapeutic approach for multifactorial liver diseases.
MeSH term(s)	Animals ; Chenodeoxycholic Acid/analogs & derivatives ; Chenodeoxycholic Acid/pharmacology ; Chenodeoxycholic Acid/therapeutic use ; Diet, High-Fat/adverse effects ; Dose-Response Relationship, Drug ; Epoxide Hydrolases/antagonists & inhibitors ; Epoxide Hydrolases/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/metabolism ; Receptors, Cytoplasmic and Nuclear/agonists ; Receptors, Cytoplasmic and Nuclear/metabolism
Chemical Substances	Receptors, Cytoplasmic and Nuclear ; obeticholic acid (0462Z4S4OZ) ; farnesoid X-activated receptor (0C5V0MRU6P) ; Chenodeoxycholic Acid (0GEI24LG0J) ; Epoxide Hydrolases (EC 3.3.2.-) ; Ephx2 protein, mouse (EC 3.3.2.10)
Language	English
Publishing date	2019-05-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2019.05.023
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Article: A SORAFENIB INDUCED MODEL OF GLOMERULAR KIDNEY DISEASE.

Stavniichuk, A / Savchuk, O / Khan, Abdul Hye / Jankiewicz, Wojciech K / Imig, John D

Visnyk Kyivs'koho natsional'noho universytetu imeni Tarasa Shevchenka. Biolohiia

2020 Volume 81, Issue 2, Page(s) 25–31

Abstract: Glomerular injury and proteinuria are important pathophysiological features of chronic kidney disease. In the present study, we provide data on a glomerular injury model that was developed using the cancer chemotherapy drug sorafenib. Sorafenib is a ... ...

Abstract	Glomerular injury and proteinuria are important pathophysiological features of chronic kidney disease. In the present study, we provide data on a glomerular injury model that was developed using the cancer chemotherapy drug sorafenib. Sorafenib is a tyrosine kinase inhibitor that acts via the vascular endothelial growth factor (VEGF) signaling pathway and is widely used to treat a variety of cancers. On the other hand, sorafenib causes serious renal side effects in patients including the development of chronic kidney disease. The current study aimed to utilize the nephrotoxic property of sorafenib to develop a rat model for chronic kidney disease. We demonstrate that rats administered sorafenib for 8 weeks along with a high salt diet (8% NaCl enriched) develop hypertension (80mmHg higher systolic blood pressure), proteinuria (75% higher), and 4-fold higher glomerular injury compared to vehicle-treated normal control rat. Sorafenib induced glomerular injury was associated with decreased (20-80% lower) renal mRNA expression of key glomerular structural proteins such as nephrin, podocin, synaptopodin, and podoplanin compared to vehicle-treated normal control rat. Renal cortical endothelial-to-mesenchymal transition (EndoMT) was activated in the sorafenib induced glomerular injury model. In the sorafenib treated rats, the renal EndoMT was evident with 20% lower mRNA expression of an endothelial marker WT-1 and 2 to 3-fold higher expression of mesenchymal markers Col III, FSP-1, α-SMA, and vimentin. In conclusion, we developed a rat pre-clinical chronic kidney disease model that manifest glomerular injury. We further demonstrate that the glomerular injury in this model is associated with decreased renal mRNA expression of key glomerular structural proteins and an activated kidney EndoMT.
Language	English
Publishing date	2020-09-29
Document type	Journal Article
DOI	10.17721/1728_2748.2020.81.25-31
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Article: THE EFFECT OF COMPOUND DM509 ON KIDNEY FIBROSIS IN THE CONDITIONS OF THE EXPERIMENTAL MODEL.

Stavniichuk, A / Savchuk, O / Khan, Abdul Hye / Jankiewicz, Wojciech K / Imig, John D / Merk, Daniel

Visnyk Kyivs'koho natsional'noho universytetu imeni Tarasa Shevchenka. Biolohiia

2020 Volume 80, Issue 1, Page(s) 10–15

Abstract: Renal fibrosis is a critical event in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Unfortunately, there are few options to target renal fibrosis in order to develop novel anti-fibrotic agents that could prevent CKD ... ...

Abstract	Renal fibrosis is a critical event in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Unfortunately, there are few options to target renal fibrosis in order to develop novel anti-fibrotic agents that could prevent CKD progression to ESRD. We evaluated the efficacy of a novel dual-acting molecule, DM509, in preventing renal fibrosis using the unilateral ureteral obstruction (UUO) renal fibrosis mouse model. DM509 acts simultaneously as a farnesoid X receptor agonist (FXRA) and a soluble epoxide hydrolase inhibitor (sEHi). In this study, groups of 8-12 weeks old C57BL/6J male mice went through either UUO or sham surgery (n=6/group). Mice were pre-treated with DM509 (10mg/kg/d) or vehicle administered in drinking water one day prior to the UUO surgery. Sham, vehicle and DM509 treatments continued until day 10 and blood and kidney tissue were collected for biochemical, histological, and gene expression analysis at the end of the treatment protocol. The UUO group exhibited kidney dysfunction with elevated blood urea nitrogen (BUN) compared to the sham group (63±7 vs. 34±6 mg/dL). DM509 treatment prevented renal dysfunction as evident from 36% lower BUN level in the DM509 treated UUO mice compared to UUO mice treated with vehicle. Vehicle treated UUO mice demonstrated renal fibrosis with elevated kidney hydroxyproline content (213±11 vs. 49±9 μg/mg protein) and kidney collagen positive area (13±2% vs. 1.1±0.1%) compared to the sham group. We found that DM509 treatment prevented renal fibrosis and DM509 treated mice had 34-66% lower levels of kidney hydroxyproline and collagen positive renal area compared to vehicle-treated UUO mice. In conclusion, our data provide evidence that the novel dual-acting FXRA and a sEHi, DM509, prevented renal dysfunction and renal fibrosis in UUO mouse model.
Language	English
Publishing date	2020-07-17
Document type	Journal Article
DOI	10.17721/1728_2748.2020.80.10-15
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Article ; Online: Loss of Chloride Channel 6 (CLC-6) Affects Vascular Smooth Muscle Contractility and Arterial Stiffness via Alterations to Golgi Calcium Stores.

Klemens, Christine A / Chulkov, Evgeny G / Wu, Jing / Hye Khan, Md Abdul / Levchenko, Vladislav / Flister, Michael J / Imig, John D / Kriegel, Alison J / Palygin, Oleg / Staruschenko, Alexander

Hypertension (Dallas, Tex. : 1979)

2021 Volume 77, Issue 2, Page(s) 582–593

Abstract: Genome-wide association studies have found a number of potential genes involved in blood pressure regulation; however, the functional role of many of these candidates has yet to be established. One such candidate gene ... ...

Abstract	Genome-wide association studies have found a number of potential genes involved in blood pressure regulation; however, the functional role of many of these candidates has yet to be established. One such candidate gene is
MeSH term(s)	Animals ; Blood Pressure/genetics ; Calcium/metabolism ; Chloride Channels/genetics ; Chloride Channels/metabolism ; Golgi Apparatus/metabolism ; Muscle Contraction/genetics ; Muscle, Smooth, Vascular/physiology ; Myocytes, Smooth Muscle/metabolism ; Rats ; Rats, Inbred Dahl ; Sodium, Dietary ; Vascular Stiffness/genetics
Chemical Substances	Chloride Channels ; Clcn6 protein, rat ; Sodium, Dietary ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.120.16589
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