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The Role of Nitric oxide/cyclic Guanosine Monophosphate (NO/cGMP) Signaling in Arteriovenous Fistula Maturation

Award Number: F31DK123977
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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PROJECT SUMMARY There are currently over 700,000 end stage renal disease (ESRD) patients in the United States. Approximately 70% of ESRD patients undergo hemodialysis as their primary kidney replacement therapy. An arteriovenous fistula (AVF) is the preferred type of vascular access in hemodialysis patients. However, nearly 60% of AVFs created develop AVF maturation failure due to early venous neointimal hyperplasia formation and impaired outward vascular remodeling. The pathological mechanisms underlying AVF maturation failure is poorly understood. Therefore, a major unmet clinical need in the field is the lack of effective therapies to treat and prevent AVF maturation failure. The central hypothesis of this study is that AVF creation will result in dysregulation of nitric oxide (NO) and cGMP activity that will disrupt proper AVF maturation by influencing AVF remodeling and neointimal hyperplasia formation. Therefore, NO/cGMP signaling pathway is an important therapeutic target for clinically successful AVF maturation. In order to study the role of NO and cGMP on AVF maturation we will 1) test the hypothesis that locally delivered NO therapy at the time of AVF creation will improve AVF maturation by inhibiting neointimal hyperplasia and enhance AVF remodeling, and reduce local inflammation; 2) test the hypothesis that a selective PDE5A inhibitor, which prevents cGMP degradation, administered before and after AVF creation, will improve AVF outward remodeling and inhibit neointimal hyperplasia; and will be also beneficial in the setting of chronic kidney disease (CKD), where AVFs are created in this clinical setting. These aims will be achieved using a rodent AVF model that has (1) an identical anatomic configuration to human AVF and (2) recapitulates the lesion of progressive venous neointimal hyperplasia seen in human AVF. Our studies are expected to elucidate the pathologic significance of NO/cGMP signaling pathway on AVF maturation as well as provide the basis to develop novel therapeutic strategies to treat and prevent AVF maturation failure in hemodialysis patients.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$5,961 )
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/15/2023	NON-COMPETING CONTINUATION	-$5,961
														Subtotal = -$5,961

Issue Date FY: 2022 ( Subtotal = $22,231 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	3	5/26/2022	NON-COMPETING CONTINUATION	-$17,787
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/29/2022	NON-COMPETING CONTINUATION	$717
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	5/23/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/4/2021	NON-COMPETING CONTINUATION	$39,302
														Subtotal = $22,231

Issue Date FY: 2021 ( Subtotal = $39,302 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/13/2020	NON-COMPETING CONTINUATION	$38,786
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/8/2021	NON-COMPETING CONTINUATION	$516
														Subtotal = $39,302

Issue Date FY: 2019 ( Subtotal = $38,282 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/24/2019	NEW	$0
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/4/2019	NEW	$38,282
														Subtotal = $38,282

Grand Total All Awards = $93,854

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The Role of Nitric oxide/cyclic Guanosine Monophosphate (NO/cGMP) Signaling in Arteriovenous Fistula Maturation

Award Number: F31DK123977

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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