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Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy
Graham Chakafana1,2, Timothy F Spracklen1,2, Stephen Kamuli1,2
1Department of Medicine, Faculty of Health Sciences, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.
Insights
Peripartum cardiomyopathy (PPCM) involves heart failure during pregnancy. Heat shock proteins (Hsps) may be key to understanding PPCM, offering potential new biomarkers and drug targets for this condition.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- Peripartum cardiomyopathy (PPCM) is a severe heart failure condition occurring late in pregnancy or postpartum.
- Current diagnostic and therapeutic options for PPCM are limited, highlighting the need for novel biomarkers and drug targets.
- Pregnancy-induced hemodynamic changes increase cardiac stress, potentially disrupting protein folding and leading to cardiac dysfunction.
Purpose of the Study:
- To investigate the role of heat shock proteins (Hsps) in the pathophysiology of Peripartum cardiomyopathy (PPCM).
- To identify potential associations between specific Hsps (Hsp70, Hsp90, small Hsps) and PPCM-related proteins.
- To explore the utility of Hsps as candidate biomarkers and therapeutic targets for PPCM.
Main Methods:
- Critical assessment of existing literature on Hsps and PPCM.
- Prediction of specific interactions between Hsps and proteins involved in PPCM.
- Exploration of Hsps as potential diagnostic markers and drug targets.
Main Results:
- Heat shock proteins (Hsps) play a critical role in maintaining cellular proteostasis under stress conditions.
- Specific Hsps, including Hsp70, Hsp90, and small Hsps, are predicted to interact with proteins implicated in PPCM.
- Hsps show promise as novel biomarkers and therapeutic targets for PPCM.
Conclusions:
- Understanding the role of Hsps in PPCM pathogenesis is crucial for improving patient outcomes.
- Hsps represent a promising area for developing new diagnostic tools and treatments for Peripartum cardiomyopathy.
- Further research into Hsps could also benefit the management of other forms of acute heart failure.
Abstract:
Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. To date, no reliable biomarkers or therapeutic interventions for the condition exist, thus necessitating an urgent need for identification of novel PPCM drug targets and candidate biomarkers. Leads for novel treatments and biomarkers are therefore being investigated worldwide. Pregnancy is generally accompanied by dramatic hemodynamic changes, including a reduced afterload and a 50% increase in cardiac output. These increased cardiac stresses during pregnancy potentially impair protein folding processes within the cardiac tissue. The accumulation of misfolded proteins results in increased toxicity and cardiac insults that trigger heart failure. Under stress conditions, molecular chaperones such as heat shock proteins (Hsps) play crucial roles in maintaining cellular proteostasis. Here, we critically assess the potential role of Hsps in PPCM. We further predict specific associations between the Hsp types Hsp70, Hsp90 and small Hsps with several proteins implicated in PPCM pathophysiology. Furthermore, we explore the possibility of select Hsps as novel candidate PPCM biomarkers and drug targets. A better understanding of how these Hsps modulate PPCM pathogenesis holds promise in improving treatment, prognosis and management of the condition, and possibly other forms of acute heart failure.
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