Cardiovascular Peptides and Myocardial Infarction
心血管肽与心肌梗塞
基本信息
- 批准号:7269302
- 负责人:
- 金额:$ 49.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-08-01 至 2010-07-31
- 项目状态:已结题
- 来源:
- 关键词:Acute myocardial infarctionAdrenergic AgentsAldosteroneAnimalsAnteriorApoptoticAreaArtsAtrial Natriuretic FactorBiologicalBiological MarkersBiologyBlood VesselsBlood capillariesCardiacCardiac MyocytesCardiovascular systemCell SurvivalCellsCollagenComplicationCoronaryCoronary ArteriosclerosisDevelopmentDilatation - actionDisruptionExcretory functionFibroblastsFibrosisFunctional disorderGenesGenetic PolymorphismGoalsHeartHeart InjuriesHeart failureHormonesHourHumanHypertensionImpairmentIntravenousKidneyLaboratory ResearchLeadMagnetic Resonance ImagingMediatingMethodologyModelingMolecularMusMutationMyocardialMyocardial InfarctionMyocardiumNatriuresisNatriuretic PeptidesNatural regenerationNuclearOutcomeOxygen ConsumptionPathological DilatationPeptidesPhasePhenotypePhosphotransferasesPhysiologicalPlasmaPreventionPropertyProteinsRenal functionRenin-Angiotensin-Aldosterone SystemReportingResearchResearch PersonnelRiskSodiumStructureSystemTherapeuticTherapeutic AgentsThinkingTimeTranslational ResearchVasodilationVasodilation disorderVentricularVentricular DysfunctionVentricular RemodelingWild Type MouseZYX geneadrenergicbasecapillarycardiogenesisclinically relevantdaydensityhuman studyinnovationmortalitymouse modelnovelpreventprogramspromoterrepairedresponsesuccess
项目摘要
DESCRIPTION (provided by applicant): Our objective is to establish that the cardiac peptide BNP is a novel and efficacious therapy for human acute myocardial infarction (AMI) to preserve myocardial structure and function. This highly translational research takes advantage of the cardioprotective and renal enhancing properties of this small and endogenous peptide in protecting the heart from injury and promoting cardiac repair. Our broad unifying hypothesis is that the endogenous natriuretic peptide (NP) system mediates cardiorenal protection and that therapeutic enhancement in experimental and human AMI with exogenous BNP will preserve myocardial structure and function while maintaining renal function. This strategy is based on the biology of BNP that enhances renal function, mediates coronary vasodilatation, reduces myocardial oxygen consumption, suppresses aldosterone release, retards adrenergic activation, induces vascular regeneration, inhibits cardiac fibroblast collagen synthesis and has anti-apoptotic properties. First, we will utilize a murine model of partial proANP gene disruption (Nppa+/-) that has clinical relevance to the recently reported human polymorphism (C664G) that is reported to be characterized by a distruption of the ANP promoter with reduced circulating ANP and risk for ventricular remodeling in human hypertension. This novel genetically altered model has normal cardiac phenotype but demonstrates an exaggerated ventricular hypertrophic and fibrotic response to AMI. In this model with AMI and in wild type (WT) mice we seek to establish cardiorenal protection with 5 days of BNP based therapy. Second, we will extend our research to human AMI investigating the cardiorenal protective properties of 72 hours of BNP therapy initiated at the time of revascularization compared to conventional therapy to preserve myocardial and renal function. Our Specific Aims are as follows: Aim 1: To characterize myocardial structure and function, humoral function and renal function in WT and Nppa+/- mice after AMI; Aim 2: To characterize myocardial structure and function, humoral function and renal function in WT and Nppa+/- mice after AMI in the presence of BNP therapy; and Aim 3: To characterize myocardial structure and function, humoral function and renal function in human AMI in the presence and absence of BNP therapy. For the public, this research may enhance long-term survival after a heart attack. The use of a hormone made in the heart and given at the time of heart attack may help the heart protect and repair itself.
描述(由申请人提供):我们的目标是建立心脏肽BNP是一种新的有效治疗人类急性心肌梗死(AMI)的方法,以保持心肌结构和功能。这项高度转化的研究利用了这种小内源性肽在保护心脏免受损伤和促进心脏修复方面的心脏保护和肾脏增强特性。我们广泛的统一假设是内源性利钠肽(NP)系统介导心肾保护,外源性BNP在实验性和人类AMI中的治疗增强将在维持肾功能的同时保护心肌结构和功能。这一策略是基于BNP的生物学特性:增强肾功能,介导冠状动脉血管舒张,降低心肌耗氧量,抑制醛固酮释放,延缓肾上腺素能激活,诱导血管再生,抑制心脏成纤维细胞胶原合成,并具有抗凋亡特性。首先,我们将利用部分proANP基因破坏(Nppa+/-)的小鼠模型,该模型与最近报道的人类多态性(C664G)具有临床相关性,该多态性的特征是ANP启动子被破坏,导致循环ANP减少,并增加高血压患者心室重构的风险。这种新的基因改变模型具有正常的心脏表型,但对AMI表现出夸大的心室肥厚和纤维化反应。在AMI模型和野生型(WT)小鼠中,我们试图通过5天的基于BNP的治疗建立心肾保护。其次,我们将把我们的研究扩展到人类AMI,研究在血运重建术时开始的72小时BNP治疗与传统治疗相比,以保护心肌和肾功能的心肾保护特性。我们的具体目的如下:目的1:研究AMI后WT和Nppa+/-小鼠心肌结构和功能、体液功能和肾功能的变化;目的2:在BNP治疗的情况下,观察AMI后WT和Nppa+/-小鼠的心肌结构和功能、体液功能和肾功能;目的3:在存在和不存在BNP治疗的情况下,表征人类AMI的心肌结构和功能、体液功能和肾功能。对于公众来说,这项研究可能会提高心脏病发作后的长期存活率。在心脏病发作时使用一种由心脏产生的激素可以帮助心脏保护和修复自己。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John C Burnett其他文献
cGMP enhancing strategies for acute and chronic heart failure
- DOI:
10.1186/1471-2210-5-s1-s22 - 发表时间:
2005-06-16 - 期刊:
- 影响因子:2.700
- 作者:
John C Burnett;Guido Boerrigter - 通讯作者:
Guido Boerrigter
Integrin receptor subtype antagonism augments BNP-mediated cGMP generation in cultured human cardiac fibroblasts: evidence for particulate guanylate cyclase receptor and integrin receptor cross-talk
- DOI:
10.1186/1471-2210-7-s1-p30 - 发表时间:
2007-07-25 - 期刊:
- 影响因子:2.700
- 作者:
Brenda K Huntley;John C Burnett - 通讯作者:
John C Burnett
Pharmacokinetic and pharmacodynamic study of a novel chimeric natriuretic peptide, CD-NP, in the normal dog
- DOI:
10.1186/1471-2210-7-s1-p38 - 发表时间:
2007-07-25 - 期刊:
- 影响因子:2.700
- 作者:
Candace YW Lee;Guido Boerrigter;Gail J Harty;John C Burnett - 通讯作者:
John C Burnett
Coadministration of B-type natriuretic peptide and the vasopressin-2 receptor antagonist tolvaptan: a novel physiologic strategy to enhance water and sodium excretion without adversely affecting renal or neurohumoral function in experimental congestive heart failure
- DOI:
10.1186/1471-2210-7-s1-p12 - 发表时间:
2007-07-25 - 期刊:
- 影响因子:2.700
- 作者:
Lisa C Costello-Boerrigter;Guido Boerrigter;Gail J Harty;John C Burnett - 通讯作者:
John C Burnett
Bioavailability of intravenous versus subcutaneous administration of the dual GC-A and GC-B designer natriuretic peptide cenderitide in healthy canines
- DOI:
10.1186/1471-2210-11-s1-p11 - 发表时间:
2011-08-01 - 期刊:
- 影响因子:2.700
- 作者:
Guido Boerrigter;Lisa C Costello-Boerrigter;Gail J Harty;John C Burnett - 通讯作者:
John C Burnett
John C Burnett的其他文献
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{{ truncateString('John C Burnett', 18)}}的其他基金
Novel Peptide Therapeutics for Cardiorenal Protection in Heart Failure
用于心力衰竭心肾保护的新型肽疗法
- 批准号:
9753353 - 财政年份:2017
- 资助金额:
$ 49.17万 - 项目类别:
Novel Peptide Therapeutics for Cardiorenal Protection in Heart Failure
用于心力衰竭心肾保护的新型肽疗法
- 批准号:
9211673 - 财政年份:2017
- 资助金额:
$ 49.17万 - 项目类别:
Protein Therapeutics to Prevent Heart Failure Post Myocardial Infarction
预防心肌梗塞后心力衰竭的蛋白质疗法
- 批准号:
8020951 - 财政年份:2010
- 资助金额:
$ 49.17万 - 项目类别:
Protein Therapeutics to Prevent Heart Failure Post Myocardial Infarction
预防心肌梗塞后心力衰竭的蛋白质疗法
- 批准号:
7867072 - 财政年份:2010
- 资助金额:
$ 49.17万 - 项目类别:
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