Low-molecular-weight heparin inhibits hypoxic pulmonary hypertension and vascular remodeling in guinea pigs

Essam Al-Ansari, Hong Kai Du, Lunyin Yu, Cristhiaan D. Ochoa, Hari G. Garg, Deborah A. Quinn, Charles A. Hales

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Rationale: We have shown previously that antiproliferative unfractionated heparins block hypoxia-induced pulmonary arterial hypertension (PAH) and vascular remodeling, and hypothesized that low-molecular-weight heparins (LMWHs) would too. Objectives: To determine the potential role and mechanisms of dalteparin and enoxaparin (two LMWHs) in inhibiting hypoxic PAH and vascular remodeling. Methods: Male Hartley guinea pigs were exposed for 10 days to normobaric 10% oxygen with dalteparin (5 mg/kg), enoxaparin (5 mg/kg), or with an equivalent volume of normal saline solution. Normoxic control animals (n = 5) received room air for 10 days. Bovine pulmonary artery smooth-muscle cells (PASMCs) were grown in 10% fetal bovine serum without heparin, with dalteparin (1 μg/mL) or with enoxaparin (1 μg/mL). Measurements: Pulmonary arterial pressure (PAP), cardiac index, right ventricular heart weight divided by left ventricular plus septum weight (RV/LV+S), hematocrit, percentage of wall thickness of intraacinar vessels (%WT-IA), percentage of wall thickness of terminal bronchiole vessels (%WT-TA), and the percentage of thick-walled vessels (%Thick) were determined. In PASMCs, expression of p27 and cell growth were compared because in mice whole heparin depends on p27 for its antiproliferative action. Main results: In hypoxic animals, hematocrit, PAP, total pulmonary vascular resistance index, RV/LV+S, %WT-IA, %WT-TA, and %Thick all rose significantly vs normoxic control animals (p < 0.05); cardiac index was unchanged. Dalteparin but not enoxaparin significantly reduced PAP, total pulmonary vascular resistance index, and RV/LV + S (p < 0.05 vs hypoxia alone); inhibited PASMC growth; and upregulated p27 expression. Enoxaparin moderately reduced vascular remodeling, which did not translate into less pulmonary hypertension. Conclusions: Not all LMWHs are the same. Dalteparin was more effective than enoxaparin in inhibiting pulmonary hypertension and vascular remodeling in hypoxic guinea pigs.

Original languageEnglish (US)
Pages (from-to)1898-1905
Number of pages8
JournalCHEST
Volume132
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

Keywords

  • Dalteparin
  • Enoxaparin
  • Hypoxia
  • Low-molecular-weight heparin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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