Related Experiment Video

Updated: Jun 26, 2026

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes
12:49

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes

Published on: September 24, 2013

Adenylyl cyclase type 5 disruption prolongs longevity and protects the heart against stress

Stephen F Vatner1, Lin Yan, Yoshihiro Ishikawa

  • 1Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Newark, NJ 07103, USA. vatnersf@umdnj.edu

Circulation Journal : Official Journal of the Japanese Circulation Society
|December 25, 2008
PubMed

Insights

Inhibition of adenylyl cyclase type 5 offers a novel therapeutic strategy for heart failure. This approach leverages stress protection and longevity observed in genetically modified mice to combat heart disease mortality.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Heart failure is a primary cause of mortality in the USA.
  • Current therapies, including ACE inhibitors and beta-blockers, have limitations.
  • Novel therapeutic strategies are needed to address heart failure.

Purpose of the Study:

  • To explore novel therapeutic approaches for heart failure.
  • To investigate the role of adenylyl cyclase type 5 in cardiac stress and longevity.
  • To evaluate adenylyl cyclase type 5 inhibition as a potential heart failure treatment.

Main Methods:

  • Development of a mouse model with genetic disruption of adenylyl cyclase type 5.
  • Assessment of lifespan and stress resistance in the modified mouse model.
  • Evaluation of protection against aging-induced, pressure overload-induced, and catecholamine-induced stresses.

Main Results:

  • Mice with disrupted adenylyl cyclase type 5 lived one-third longer than wild-type mice.
  • These mice exhibited protection against various cardiac stress models.
  • Genetic disruption of adenylyl cyclase type 5 demonstrated a link between the enzyme and cardiac health.

Conclusions:

  • Adenylyl cyclase type 5 plays a critical role in cardiac stress response and longevity.
  • Inhibition of adenylyl cyclase type 5 presents a promising new therapeutic strategy for heart failure.
  • Targeting adenylyl cyclase type 5 could offer a novel approach to managing heart failure.

More Related Videos

Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk05:15

Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk

Published on: July 27, 2022

Transverse Aortic Constriction in Mice08:25

Transverse Aortic Constriction in Mice

Published on: April 21, 2010

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...