The Protective Role of the Long Pentraxin PTX3 in Spontaneously Hypertensive Rats with Heart Failure

Cardiovasc Toxicol. 2021 Oct;21(10):808-819. doi: 10.1007/s12012-021-09671-0. Epub 2021 Jun 25.

Abstract

Pentraxin 3 (PTX3) is synthesized locally and released into the circulation, reflecting local inflammation in the cardiovascular system. Therefore, we conducted a study to explore the effect of PTX3 in spontaneously hypertensive heart failure (SHHF) rats. Sprague Dawley (SD) and SHHF rats were treated with recombinant PTX3 protein, and the blood pressure (BP) and echocardiographic parameters were collected. Radioimmunoassay, enzyme immunoassay and enzyme-linked immunosorbent assay (ELISA) were applied to detect plasma levels of atrial/B-type natriuretic peptide (ANP/BNP) and PTX3. The pathological changes in the myocardial tissues were observed by hematoxylin and eosin (HE) and Masson stainings. The mRNA and protein expressions were detected by quantitative real-time reverse-transcription polymerase chain reaction (qPCR) and western blotting. Cardiomyocyte apoptosis was evaluated by TUNEL staining and DNA fragmentation test. Increased plasma concentrations of PTX3 were found in SHHF rats compared with SD rats, which was further enhanced by recombinant PTX3 protein. After injection with recombinant PTX3 protein, the heart function was improved in SHHF rats with the decreased systolic and diastolic BP, and the reduced plasma levels of ANP and BNP. Moreover, PTX3 improved the myocardial damage and interstitial fibrosis in SHHF rats with reduced cardiomyocyte apoptosis and decreased mRNA expressions of pro-inflammatory factors in myocardial tissues. PTX3 could decrease the BP and plasma levels of ANP and BNP in SHHF rats, as well as improve the inflammation, cardiomyocyte apoptosis, and pathological changes of myocardial tissues, suggesting it may be a useful intervention in the treatment of SHHF.

Keywords: Heart failure; Hypertension; Pentraxin 3.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Atrial Natriuretic Factor / blood
  • Blood Pressure / drug effects*
  • C-Reactive Protein / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Natriuretic Peptide, Brain / blood
  • Rats
  • Rats, Inbred SHR
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Serum Amyloid P-Component / pharmacology*
  • Ventricular Function, Left / drug effects

Substances

  • Cytokines
  • Recombinant Proteins
  • Serum Amyloid P-Component
  • Natriuretic Peptide, Brain
  • PTX3 protein
  • Atrial Natriuretic Factor
  • C-Reactive Protein