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Expression of High Mobility Group Protein B1 in Cardiac Tissue of Elderly Patients with Coronary Artery Disease with

Mei Bruton1, Ivana Hollan, Julie Xiao

  • 1Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.

Gerontology
|April 21, 2017
PubMed

Insights

Elderly patients with inflammatory rheumatic diseases (IRD) show increased high mobility group protein B1 (HMGB1) release in heart cells, suggesting HMGB1 pathways may drive cardiovascular disease risk in these individuals.

Area of Science:

  • Cardiovascular Medicine
  • Rheumatology
  • Molecular Biology

Background:

  • Elderly patients with inflammatory rheumatic diseases (IRD) have a higher risk of cardiovascular diseases (CVD) like coronary artery disease (CAD) and heart failure.
  • The underlying molecular mechanisms linking IRD and CVD remain unclear.
  • High mobility group protein B1 (HMGB1) has been implicated in myocardial dysfunction when released from cardiomyocyte nuclei.

Purpose of the Study:

  • To determine if HMGB1 and its receptors are present in the cardiac muscle of elderly patients with CAD.
  • To compare HMGB1 expression in patients with and without concomitant IRD.

Main Methods:

  • Immunohistochemistry was used to examine HMGB1 and its receptors (receptor for advanced glycation end products, TLR2, TLR4) in myocardial biopsies from 18 elderly CAD patients (10 with IRD, 8 without).
  • Western blot analysis quantified total HMGB1 protein levels in cardiac biopsies from 10 patients (5 with IRD, 5 without).

Main Results:

  • Pathologic cytosolic HMGB1 was abundant in cardiomyocytes of all IRD patients, but minimally present in non-IRD patients.
  • Total HMGB1 protein levels were lower in myocardial biopsies from IRD patients compared to non-IRD patients.
  • All three HMGB1 receptors were expressed in cardiomyocytes across all patient groups.

Conclusions:

  • Increased cytosolic HMGB1 and reduced total HMGB1 in IRD patients suggest greater HMGB1 release from myocardial nuclei.
  • HMGB1 signaling pathways may be activated in elderly CAD patients with IRD, promoting inflammation and cardiovascular issues.
  • Targeting HMGB1 could potentially mitigate cardiovascular event risk in IRD patients.
Abstract

Keywords:
Coronary artery diseaseHigh mobility group protein B1Inflammatory rheumatic diseases

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