Related Experiment Video

Updated: Mar 25, 2026

Preparation of Human Myocardial Tissue for Long-Term Cultivation
10:58

Preparation of Human Myocardial Tissue for Long-Term Cultivation

Published on: June 2, 2022

6.0K

Expressing an inhibitor of PLCβ1b sustains contractile function following pressure overload

David R Grubb1, Xiao-Ming Gao1, Helen Kiriazis1

  • 1Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne 3004, Victoria, Australia.

Journal of Molecular and Cellular Cardiology
|February 25, 2016
PubMed

Insights

Inhibition of phospholipase Cβ1b (PLCβ1b) in the heart prevents cardiac dysfunction and improves survival after pressure overload. This targeted approach offers a new therapeutic strategy for heart failure.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Phospholipase Cβ1b (PLCβ1b) activity is elevated in heart failure and contributes to cardiac dysfunction.
  • PLCβ1b's role in the sarcolemma is critical for its pathological effects.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting PLCβ1b in a cardiac pressure overload model.
  • To assess the efficacy of a novel peptide inhibitor (PLCβ1b-CT) delivered via adeno-associated virus (rAAV6-PLCβ1b-CT).

Main Methods:

  • Adeno-associated virus (rAAV6-PLCβ1b-CT) expressing a PLCβ1b inhibitory peptide was administered intravenously.
  • Trans-aortic constriction (TAC) or sham surgery was performed 8 weeks post-administration.
  • Cardiac function, lung congestion, survival, and hypertrophy were evaluated.

Main Results:

  • rAAV6-PLCβ1b-CT expression prevented loss of contractile function and reduced lung congestion following TAC.
  • Survival was improved in TAC mice treated with the inhibitor.
  • PLCβ1b inhibition attenuated hypertrophy and improved cardiac function when administered even after TAC onset.

Conclusions:

  • Targeted inhibition of sarcolemmal PLCβ1b ameliorates pathological responses to acute pressure overload.
  • PLCβ1b inhibition represents a promising new class of inotropic agents for treating heart failure.
Keywords:
Cardiac hypertrophyHeart failureInotropic agentMouse

More Related Videos

Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes08:39

Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Published on: December 22, 2020

4.8K
Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice06:22

Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice

Published on: September 17, 2015

15.6K

Related Concept Videos

Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
2.2K
Heart Failure Drugs: β-Blockers01:22

Heart Failure Drugs: β-Blockers

β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
1.1K
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
9.2K
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
1.8K
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...
6.9K
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
6.7K