Targeting Collagen Pathways as an HFpEF Therapeutic Strategy

Area of Science:

• Cardiology
• Biochemistry
• Pathophysiology

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a growing clinical challenge with increasing prevalence.
• Current treatments lack efficacy, necessitating personalized therapeutic strategies beyond the one-size-fits-all approach used for heart failure with reduced ejection fraction (HFrEF).
• Alterations in collagen quantity and quality are implicated in cardiac remodeling and fibrosis within HFpEF.

Purpose of the Study:

• To review the mechanisms of collagen alterations in cardiac fibrosis relevant to HFpEF.
• To identify potential therapeutic targets for cardiac fibrosis in HFpEF patients.

Main Methods:

• Review of existing literature on collagen cross-linking mechanisms (enzymatic and non-enzymatic) in cardiac fibrosis.
• Examination of the role of protease-activated receptor-1 (PAR1) and transforming growth factor-β (TGF-β) signaling in enzymatic fibrosis.
• Analysis of sodium glucose co-transporter type 2 inhibitors (SGLT2is) in counteracting non-enzymatic fibrosis via advanced glycation end-products (AGEs).

Main Results:

• Enzymatic inhibition of PAR1 and TGF-β signaling reduced cardiac fibrosis in murine models.
• SGLT2 inhibitors demonstrated potential in mitigating ventricular remodeling by counteracting AGE deposition.
• Both enzymatic and non-enzymatic collagen cross-linking pathways are critical in HFpEF pathophysiology.

Conclusions:

• Targeting collagen cross-linking mechanisms presents a promising avenue for novel HFpEF therapies.
• Personalized treatment strategies focusing on specific fibrotic pathways are crucial for managing HFpEF.
• Further research into enzymatic and non-enzymatic fibrosis targets could lead to improved patient outcomes in HFpEF.