The Glycobiology of Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease of complex etiology. Cases of PAH that do not receive therapy after diagnosis have a low survival rate. Multiple reports have shown that idiopathic PAH, or IPAH, is associated with metabolic dysregulation including altered bioavailability of nitric oxide (NO) and dysregulated glucose metabolism. Multiple processes such as increased proliferation of pulmonary vascular cells, angiogenesis, apoptotic resistance, and vasoconstriction may be regulated by the metabolic changes demonstrated in PAH. Recent reports have underscored similarities between metabolic abnormalities in cancer and IPAH. In particular, increased glucose uptake and altered glucose utilization have been documented and have been linked to the aforementioned processes. We were the first to report a link between altered glucose metabolism and changes in glycosylation. Subsequent reports have highlighted similar findings, including a potential role for altered metabolism and aberrant glycosylation in IPAH pathogenesis. This review will detail research findings that demonstrate metabolic dysregulation in PAH with an emphasis on glycobiology. Furthermore, this report will illustrate the similarities in the pathobiology of PAH and cancer and highlight the novel findings that researchers have explored in the field.

Keywords: glycobiology; metabolism; pulmonary hypertension.

Figure 1

The glycobiology of PAH. Changes in glycosylation have been linked to dysregulated cellular metabolism, a hallmark of both PAH and cancer. Galectins (Lectins); O-GlcNAc and sialylation (Terminal Glycosylation); as well as hyaluronan, perlecan, versican, aggrecan, and syndecan (Proteoglycans and Glycosaminoglycans) have been investigated in PAH.