Journal article
An injectable microparticle formulation provides long-term inhibition of hypothalamic ERK1/2 activity and sympathetic excitation in rats with heart failure
Molecular pharmaceutics, Vol.17(9), pp.3643-3648
09/08/2020
DOI: 10.1021/acs.molpharmaceut.0c00501
PMID: 32786958
Abstract
Sympathetic excitation contributes to clinical deterioration in systolic heart failure (HF). Significant inhibition of hypothalamic paraventricular nucleus (PVN) ERK1/2 signaling and a subsequent reduction of plasma norepinephrine (NE) levels in HF rats were achieved two weeks after a single subcutaneous injection of PD98059-loaded polymeric microparticles, without apparent adverse events, while blank microparticles had no effect. Similar reductions in plasma NE, a general indicator of sympathetic excitation, were previously achieved in HF rats by intracerebroventricular infusion of PD98059 or genetic knockdown of PVN ERK1/2 expression. This study presents a clinically feasible therapeutic approach to the central abnormalities contributing to HF progression.
Details
- Title: Subtitle
- An injectable microparticle formulation provides long-term inhibition of hypothalamic ERK1/2 activity and sympathetic excitation in rats with heart failure
- Creators
- Youssef W Naguib - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA 52242Yang Yu - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA 52242Shun-Guang Wei - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA 52242Angie Morris - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA 52242Brittany E Givens - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA 52242Aml I Mekkawy - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA 52242Robert M Weiss - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA 52242Robert B Felder - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA 52242Aliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA 52242
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.17(9), pp.3643-3648
- DOI
- 10.1021/acs.molpharmaceut.0c00501
- PMID
- 32786958
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Grant note
- DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs; DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute, award: R01-HL-096671, R01-HL-136149; DOI: 10.13039/100000879, name: Alfred P. Sloan Foundation; DOI: 10.13039/100008893, name: University of Iowa; DOI: 10.13039/100007496, name: Biomedical Laboratory Research and Development, VA Office of Research and Development; DOI: 10.13039/100000179, name: Office of the Director, award: S10-OD-019941; name: Lyle and Sharon Bighley; name: National GEM Consortium
- Language
- English
- Date published
- 09/08/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Internal Medicine
- Record Identifier
- 9984070794302771
Metrics
38 Record Views