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Haptoglobin deficiency causes cardiac rupture and adverse remodeling after myocardial infarction

Acute Coronary Syndromes (ACS)




Fatih Arslan, FESC
  Presenter
Presenter Play presentation webcast
Arslan, Fatih
(Netherlands)

List of Authors:
Fatih Arslan, Mirjam B. Smeets, Lars Akeroyd, Leo Timmers, Ben van Middelaar, Krista den Ouden, Gerard Pasterkamp, Sai Kiang Lim & Dominique P.V. de Kleijn

Abstract:

Background
Decreased haptoglobin (Hp) functionality due to allelic variations is associated with worsened outcome in patients after myocardial infarction (MI). However, mechanistic insight onto the role of Hp in response to MI and adverse remodeling is lacking.
In the present study, we describe for the first time that haptoglobin is critically involved in both early and late cardiac repair responses via PAI-1 and collagen synthesis after MI.

Methods and Results
Left coronary artery ligation was performed in Hp-/- and wild-type (WT) mice. Death rate was significantly higher in Hp-/- mice (63% vs. 20% in WT mice), commonly caused by cardiac rupture in Hp-/- animals. Histological analysis of 3 and 7 days old infracted hearts revealed more frequent and more severe intramural hemorrhage in Hp-/- mice and disorganized granulation tissue. In addition, PAI-1 activity was reduced in Hp-/- animals (3.53(0.76 vs. 1.50±0.17, p=0.022).
Despite similar infarct size, Hp-/- mice exhibited more expansive remodeling and worsened systolic performance during follow-up as assessed by cardiac-MRI. Fibronectin transcription was highly reduced in Hp-/- mice at all time-points, suggesting impaired post-infarct provisional matrix formation. At 28 days post-MI, lack of Hp was associated with reduced collagen deposition and synthesis in the infarct area, without affecting de novo capillary and small vessel formation in the peri-infarct zone.

Conclusions
Haptoglobin deficiency severely deteriorates tissue repair and cardiac performance after experimental MI. Haptoglobin appears to play a pivotal role in both short- and long-term tissue repair responses presumably via PAI-1 activity and fibronectin and collagen production, respectively.

References


712005

SessionTitle:

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The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.