HMGB1: a multifaceted mediator of cell death pathways in cardiovascular diseases

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiology

Background:

• Cardiovascular diseases (CVDs) are a major global cause of mortality, significantly impacting life expectancy and healthcare costs.
• High mobility group box 1 (HMGB1) is a multifunctional protein implicated in various cell death mechanisms relevant to CVDs.
• HMGB1's role shifts from beneficial early-stage immune response to detrimental disruption of cellular homeostasis with disease progression.

Purpose of the Study:

• To elucidate the complex role of High mobility group box 1 (HMGB1) in cardiovascular disease pathogenesis.
• To investigate HMGB1's involvement in diverse cell death pathways, including PANoptosis, ferroptosis, and efferocytosis.
• To assess the therapeutic potential of targeting HMGB1 in cardiovascular pathologies.

Main Methods:

• Review of preclinical studies and existing literature on HMGB1 function in cardiovascular disease models.
• Analysis of HMGB1's impact on the balance between autophagy and apoptosis.
• Investigation of HMGB1's role in cellular homeostasis and response to injury.

Main Results:

• HMGB1 accumulation disrupts the balance between autophagy and apoptosis in progressing CVDs.
• Excessive HMGB1 is linked to multiple cell death types, including PANoptosis, ferroptosis, and efferocytosis.
• Preclinical studies confirm HMGB1 as a viable therapeutic target for CVDs.

Conclusions:

• Understanding HMGB1's regulatory functions is key to developing targeted cardiovascular therapies.
• Targeting HMGB1 release and expression shows therapeutic promise in CVD models.
• Combined therapeutic strategies involving HMGB1 may advance CVD treatment.