RGD Reference Report - Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.

General

Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.
Authors:	Arnold, AS Tang, YL Qian, K Shen, L Valencia, V Phillips, MI Zhang, YC
Citation:	Arnold AS, etal., J Hypertens. 2007 Jan;25(1):197-205.
RGD ID:	7241557
Pubmed:	PMID:17143192 (View Abstract at PubMed)
DOI:	DOI:10.1097/01.hjh.0000254374.73241.ab (Journal Full-text)
OBJECTIVES: Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. METHODS: To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. RESULTS: One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. CONCLUSIONS: The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR.

RGD Manual Disease Annotations Click to see Annotation Detail View

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Left Ventricular Hypertrophy		ISO	Adrb1 (Rattus norvegicus)	7241557; 7241557		RGD
Left Ventricular Hypertrophy		IMP		7241557		RGD
myocardial infarction		ISO	Adrb1 (Rattus norvegicus)	7241557; 7241557		RGD
myocardial infarction		IMP		7241557		RGD

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of apoptotic process		IMP		7241557		RGD

Objects Annotated

Genes (Rattus norvegicus)

Adrb1 (adrenoceptor beta 1)

Genes (Mus musculus)

Adrb1 (adrenergic receptor, beta 1)

Genes (Homo sapiens)

ADRB1 (adrenoceptor beta 1)

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Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.