Targeting the cytoskeleton and extracellular matrix in cardiovascular disease drug discovery

Area of Science:

• Cardiovascular biology
• Cellular and molecular medicine
• Drug discovery

Background:

• Current cardiovascular disease (CVD) drug discovery primarily targets inflammation and immunopathology.
• Emerging research highlights the roles of cytoskeletal and extracellular matrix (ECM) proteins in CVD phenotypes like cardiac fibrosis and coronary artery disease.
• The efficacy of anti-inflammatory drugs targeting microtubule polymerization suggests therapeutic potential in cardiac cytoskeleton and ECM.

Purpose of the Study:

• To review the dynamic roles of the cytoskeleton and ECM in cardiovascular disease (CVD) pathophysiology.
• To identify novel therapeutic targets within cytoskeletal and ECM-related genes.
• To explore the potential for therapeutics that modulate cellular architecture in plaque formation, rupture, and cardiac contractility.

Main Methods:

• Literature review focusing on cytoskeletal and ECM proteins in CVD.
• Analysis of existing findings on therapeutic targets like gelsolin and calponin 2.
• Examination of the structural interplay between the cytoskeleton and ECM.

Main Results:

• The cytoskeleton and ECM are implicated in diverse CVDs, including cardiac fibrosis and coronary artery disease.
• Matricellular proteins, such as tenascin-C, regulate the cellular microenvironment in CVD.
• Proteins like gelsolin and calponin 2 are pivotal in plaque development and represent potential therapeutic targets.

Conclusions:

• The cardiac cytoskeleton and associated ECM proteins represent a promising area for novel cardiovascular disease (CVD) target discovery.
• The interconnectedness of the cytoskeleton and ECM offers a dual approach for therapeutic target evaluation.
• Targeting cytoskeletal and ECM regulation may lead to new therapeutics for altering cellular architecture and treating CVDs.