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Journal of Cardiovascular Translational Research

, Volume 8, Issue 9, pp 554–566 | Cite as

Serum Amyloid P-Component Prevents Cardiac Remodeling in Hypertensive Heart Disease

  • Stephen J. Horgan
  • Chris J. Watson
  • Nadia Glezeva
  • Pat Collier
  • Roisin Neary
  • Isaac J. Tea
  • Niamh Corrigan
  • Mark Ledwidge
  • Ken McDonald
  • John A. Baugh
Article

Abstract

The potential for serum amyloid P-component (SAP) to prevent cardiac remodeling and identify worsening diastolic dysfunction (DD) was investigated. The anti-fibrotic potential of SAP was tested in an animal model of hypertensive heart disease (spontaneously hypertensive rats treated with SAP [SHR − SAP] × 12 weeks). Biomarker analysis included a prospective study of 60 patients with asymptomatic progressive DD. Compared with vehicle-treated Wistar-Kyoto rats (WKY-V), the vehicle-treated SHRs (SHR-V) exhibited significant increases in left ventricular mass, perivascular collagen, cardiomyocyte size, and macrophage infiltration. SAP administration was associated with significantly lower left ventricular mass (p < 0.01), perivascular collagen (p < 0.01), and cardiomyocyte size (p < 0.01). Macrophage infiltration was significantly attenuated in the SHR-SAP group. Biomarker analysis showed significant decreases in SAP concentration over time in patients with progressive DD (p < 0.05). Our results indicate that SAP prevents cardiac remodeling by inhibiting recruitment of pro-fibrotic macrophages and that depleted SAP levels identify patients with advancing DD suggesting a role for SAP therapy.

Keywords

Serum amyloid P-component Hypertensive heart disease Left ventricular remodeling Macrophages Spontaneously hypertensive rats 

Notes

Compliance with Ethical Standards

Sources of Funding

This work was supported by the Health Research Board of Ireland [Research Training Fellowship for Healthcare Professionals] and the Irish Heart Foundation [Noel Hickey Bursary].

Disclosures

Stephen Horgan reports receiving a government non-profit research training fellowship grant for healthcare professionals from the Health Research Board of the Irish Government. All authors disclose that the Heartbeat Trust received unrestricted educational and/or research grants from Pfizer, Merck Sharp and Dohme, A. Menarini, Alere, Roche, Takeda, Abbott, Servier and the European Commission Framework Programme 7 MEDIA Project. Mark Ledwidge and Kenneth McDonald report receiving speaking/consulting fees from Servier, Pfizer, Alere, Roche and Merck (all based in Ireland) and a government non-profit grant from the Health Research Board of the Irish Government. Mark Ledwidge is co-founder and shareholder of University spin-out Solvotrin Therapeutics which is developing aspirin/niacin prodrugs. Kenneth McDonald is a shareholder of Solvotrin.

Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Study

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

Supplementary material

12265_2015_9661_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 22 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Stephen J. Horgan
    • 1
    • 2
  • Chris J. Watson
    • 1
    • 2
  • Nadia Glezeva
    • 1
    • 2
  • Pat Collier
    • 1
    • 2
    • 3
  • Roisin Neary
    • 1
  • Isaac J. Tea
    • 1
  • Niamh Corrigan
    • 1
  • Mark Ledwidge
    • 1
    • 2
  • Ken McDonald
    • 1
    • 2
  • John A. Baugh
    • 1
  1. 1.UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of MedicineUniversity College DublinDublinIreland
  2. 2.Chronic Cardiovascular Disease UnitSt. Vincent’s University HospitalDublin 4Ireland
  3. 3.Cardiovascular MedicineCleveland ClinicClevelandUSA

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