Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction
Background The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.032646 |
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| author | Jake E. Doiron Zhen Li Xiaoman Yu Kyle B. LaPenna Heather Quiriarte Timothy D. Allerton Kashyap Koul Andrew Malek Sanjiv J. Shah Thomas E. Sharp Traci T. Goodchild Daniel R. Kapusta David J. Lefer |
| author_facet | Jake E. Doiron Zhen Li Xiaoman Yu Kyle B. LaPenna Heather Quiriarte Timothy D. Allerton Kashyap Koul Andrew Malek Sanjiv J. Shah Thomas E. Sharp Traci T. Goodchild Daniel R. Kapusta David J. Lefer |
| author_sort | Jake E. Doiron |
| collection | DOAJ |
| description | Background The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. Methods and Results Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF‐RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF‐RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF‐RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF‐RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial‐dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1β, and expression of profibrotic mediators. RF‐RDN failed to exert beneficial effects when administered in the 20‐week‐old HFpEF cohort. Conclusions Our data demonstrate that early RF‐RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF‐RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease. |
| first_indexed | 2024-03-07T23:33:19Z |
| format | Article |
| id | doaj.art-377b6dd424934dd9a1525c1d2e497cee |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2025-02-18T07:48:09Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-377b6dd424934dd9a1525c1d2e497cee2024-11-05T14:15:40ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-02-0113410.1161/JAHA.123.032646Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection FractionJake E. Doiron0Zhen Li1Xiaoman Yu2Kyle B. LaPenna3Heather Quiriarte4Timothy D. Allerton5Kashyap Koul6Andrew Malek7Sanjiv J. Shah8Thomas E. Sharp9Traci T. Goodchild10Daniel R. Kapusta11David J. Lefer12Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Sciences Center New Orleans LA USADepartment of Cardiac Surgery Smidt Heart Institute, Cedars‐Sinai Medical Center Los Angeles CA USADepartment of Cardiac Surgery Smidt Heart Institute, Cedars‐Sinai Medical Center Los Angeles CA USADepartment of Pharmacology and Experimental Therapeutics Louisiana State University Health Sciences Center New Orleans LA USADepartment of Vascular Metabolism Pennington Biomedical Research Center Baton Rouge LA USADepartment of Vascular Metabolism Pennington Biomedical Research Center Baton Rouge LA USASchool of Medicine Louisiana State University Health Sciences Center New Orleans New Orleans LA USASchool of Medicine Louisiana State University Health Sciences Center New Orleans New Orleans LA USADivision of Cardiology, Department of Medicine and Bluhm Cardiovascular Institute Northwestern University Feinberg School of Medicine Chicago IL USADepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine University of South Florida Tampa FL USADepartment of Cardiac Surgery Smidt Heart Institute, Cedars‐Sinai Medical Center Los Angeles CA USADepartment of Pharmacology and Experimental Therapeutics Louisiana State University Health Sciences Center New Orleans LA USADepartment of Cardiac Surgery Smidt Heart Institute, Cedars‐Sinai Medical Center Los Angeles CA USABackground The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. Methods and Results Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF‐RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF‐RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF‐RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF‐RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial‐dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1β, and expression of profibrotic mediators. RF‐RDN failed to exert beneficial effects when administered in the 20‐week‐old HFpEF cohort. Conclusions Our data demonstrate that early RF‐RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF‐RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.https://www.ahajournals.org/doi/10.1161/JAHA.123.032646heart failureHFpEFNLRP3 inflammasomerenal denervationsympathetic nervous system |
| spellingShingle | Jake E. Doiron Zhen Li Xiaoman Yu Kyle B. LaPenna Heather Quiriarte Timothy D. Allerton Kashyap Koul Andrew Malek Sanjiv J. Shah Thomas E. Sharp Traci T. Goodchild Daniel R. Kapusta David J. Lefer Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease heart failure HFpEF NLRP3 inflammasome renal denervation sympathetic nervous system |
| title | Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction |
| title_full | Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction |
| title_fullStr | Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction |
| title_full_unstemmed | Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction |
| title_short | Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction |
| title_sort | early renal denervation attenuates cardiac dysfunction in heart failure with preserved ejection fraction |
| topic | heart failure HFpEF NLRP3 inflammasome renal denervation sympathetic nervous system |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.032646 |
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