Targeting cardiac hypertrophy: toward a causal heart failure therapy

Area of Science:

• Cardiology
• Molecular Biology
• Pharmacology

Background:

• Cardiac hypertrophy results from hemodynamic or metabolic stress, indicating maladaptive cellular processes and disease progression.
• It serves as a key marker for cardiac remodeling, with its regulatory pathways offering therapeutic targets.
• Understanding these pathways is crucial for developing treatments to slow disease progression and improve patient outcomes.

Purpose of the Study:

• To review hypertrophic signaling pathways in cardiomyocytes.
• To discuss established and novel pharmacological targets for intervention.
• To highlight emerging experimental treatment concepts for cardiac hypertrophy.

Main Methods:

• Review of scientific literature on cardiomyocyte hypertrophic signaling.
• Discussion of current and pipeline pharmacological agents.
• Overview of experimental therapeutic strategies.

Main Results:

• Identified novel drug candidates including third-generation aldosterone antagonists and biased angiotensin II receptor agonists.
• Highlighted clinical trials evaluating cGMP-dependent signaling stimulation, such as Angiotensin Receptor-Neprilysin Inhibitors (ARNi).
• Discussed emerging therapies like Ca-mediated transcriptional regulation inhibition, gene therapy (SERCA2a, PI3K), and microRNA-based treatments.

Conclusions:

• Antihypertrophic therapy extends beyond blocking classical signaling cascades (β-adrenergic, renin-angiotensin-aldosterone system).
• Novel therapeutic approaches require further clinical validation to confirm their impact on patient outcomes.
• Targeting specific cellular pathways offers a promising avenue for managing cardiac hypertrophy.