Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Lin, King‐Fu; Chao, Julie; Chao, Lee

doi:10.1161/01.hyp.33.1.219

Cited by 43 publications

(27 citation statements)

References 39 publications

(26 reference statements)

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“…Consequently, gene therapy represents a treatment modality in which ANP could be applied to a chronic disorder such as HTN. ANP gene therapy has been studied in rat models of HTN with positive but limited results (8,9). Certainly, physiologic results presented here are in accord with results obtained in these previous studies, as significant decreases in systolic blood pressure were seen in mice expressing ANP from iANP.HD.…”

Section: Discussionsupporting

confidence: 88%

“…Prior attempts at using ANP for the gene therapy of HTN suffered from limitations, such as short duration of ANP expression and lack of control of ANP expression subsequent to vector delivery (9). iANP.HD, the HD-Ad vector used throughout the studies described here, was designed to address the limitations of earlier ANP gene-therapy approaches.…”

Section: Resultsmentioning

confidence: 99%

“…Studies involving the infusion of synthetic ANP to humans with HTN have demonstrated significant decreases in blood pressure and brisk natriuresis͞diuresis associated with peptide administration (6, 7). Likewise, genetherapy experiments conducted with adenoviral vectors in rodent models of HTN have shown equally impressive results (8,9). However, these studies also have revealed the serious limitations that are associated with the use of ANP in a gene-therapy context.…”

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confidence: 99%

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Regulatable atrial natriuretic peptide gene therapy for hypertension

Schillinger

Tsai

Taffet

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Hypertension (HTN) is a disease that begins with dysfunctional renal-sodium excretion and progresses to a syndrome of highly elevated systolic, diastolic, and mean arterial pressures. Inadequacies in the therapy of HTN have led to the investigation of the gene therapy of this disease by using systemic overproduction of vasodilatory peptides, such as atrial natriuretic peptide (ANP). However, gene-therapy approaches to HTN using ANP are limited by the need for long-term ANP gene expression and, most important, control of ANP gene expression. Here, we introduce a helperdependent adenoviral vector carrying the mifepristone (Mfp)-inducible gene-regulatory system to control in vivo ANP expression. In the BPH͞2 mouse model of HTN, Mfp-inducible ANP expression was seen for a period of >120 days after administration of vector. Physiological effects of ANP, including decreased systolic blood pressure, increased urinary cGMP output, and decreases in heart weight as a percentage of body weight were also under the control of Mfp. Given these capabilities, this vector represents a paradigm for the gene therapy of HTN. adenovirus ͉ mifepristone-inducible H ypertension (HTN) is a disease that is characterized by chronically elevated arterial blood pressure that affects Ϸ25-35% of the population in developed countries, and it is one of the leading causes of morbidity and mortality in adults (1). Development of HTN is likely to involve defects in renal-sodium handling that are exacerbated by maladaptive activation of neurohormonal compensatory mechanisms. The morbidity and mortality caused by the hypertensive state are a consequence of detrimental effects that manifest predominantly in the heart, brain, and kidney and are referred to collectively as hypertensive end-organ disease. Typically, endorgan disease involves pathological left-ventricular hypertrophy, a propensity toward cerebrovascular accidents, and accelerated renal atherosclerosis (1, 2).The current therapy of HTN has been rationally designed to address the recognized causes of hypertensive pathophysiology, including impaired urinary-sodium excretion and neurohormonal compensatory-mechanism activation. Also, in recognition of the fact that hypertensive end-organ disease represents the true danger of chronically elevated arterial blood pressure, the main goals of antihypertensive therapy have evolved to include a reduction in blood pressure as well as prevention of cardiovascular, cerebrovascular, and renal pathology associated with elevated blood pressure (2, 3). However, a multitude of studies have revealed that no available drug therapy for HTN has the capability to cure the hypertensive state or reverse or prevent the pathological changes associated with hypertensive end-organ disease fully (2). As a result, therapeutic approaches to HTN involving gene therapy have been of recent interest.Atrial natriuretic peptide (ANP), a 27-aa peptide hormone with potent vasodilatory, natriuretic, diuretic, and antihypertrophic effects, is an attractive candidate gene product f...

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulatable atrial natriuretic peptide gene therapy for hypertension

Schillinger

Tsai

Taffet

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…42,43 ANP gene delivery attenuated HT, cardiac hypertrophy, and renal injury, 42 as well as decreased the stroke death rate and the thickness of the aortic wall. 43 Therefore, ANP gene delivery has therapeutic potential for HT and possibly other cardiac and renal disease states, but further studies are warranted.…”

Section: Anp Gene Deliverymentioning

confidence: 99%

Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―

Ichiki¹,

Burnett²

2017

Circ J

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With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF). Human genomics has strengthened our understanding of ANP, revealing specific ANP gene variants that may be associated with biological dysfunction, but also may mediate protective properties, including in metabolic syndrome. Advances in understanding the processing and degradation of ANP molecular forms have resulted in therapeutic breakthroughs, especially inhibition of ANP degradation by neprilysin inhibitors. Although ANP is administered intravenously for acute HF, a novel therapeutic strategy is its chronic delivery by subcutaneous injection. An innovative therapeutic development is engineering to develop ANP-based peptides for chronic use. These interconnected topics of ANP biology and therapeutics will be reviewed in detail.

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“…Novel targets include disorders without effective standard therapies, such as pulmonary hypertension (11) as well as more prevalent disorders such as systemic hypertension and congestive heart failure (5,17,18). Ultimately, the prevention of atherosclerosis, the proximate cause of myocardial infarction, limb ischemia, and stroke may be the most important target for gene transfer.…”

Section: The Current State Of Cardiovascular Gene Transfermentioning

confidence: 99%

What can cardiovascular gene transfer learn from genomics: and vice versa?

Kim

Skelding

Nabel

et al. 2002

Physiological Genomics

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The field of gene transfer has developed in an era of expanding biomedical knowledge. The potential for gene transfer to treat cardiovascular disease is great, yet identified and unidentified barriers remain. Gene transfer and its ultimate application, gene therapy, require extensive details of not only the mechanism of disease but the biological implications of the vectors used to deliver the therapeutic genes as well. Many of these details are becoming available via the study of genomics. Genomics, the study of complete genetic sequences, holds the potential for enabling and amplifying the therapeutic hopes for gene transfer. Identification of new therapeutic genes, new regulatory sequences, and establishing the patterns of gene expression from tissues exposed to vectors and transgenes will rapidly advance the application of gene transfer. Finally, there are historical and ongoing lessons learned from the development of gene transfer that may be applicable to the challenging field of genomics and may enable its future success.

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Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Cited by 43 publications

References 39 publications

Regulatable atrial natriuretic peptide gene therapy for hypertension

Regulatable atrial natriuretic peptide gene therapy for hypertension

Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―

What can cardiovascular gene transfer learn from genomics: and vice versa?

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Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Cited by 43 publications

References 39 publications

Regulatable atrial natriuretic peptide gene therapy for hypertension

Regulatable atrial natriuretic peptide gene therapy for hypertension

Atrial Natriuretic Peptide ― Old But New Therapeutic in Cardiovascular Diseases ―

What can cardiovascular gene transfer learn from genomics: and vice versa?

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Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―