Soluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls (p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls.

The relationship between tooth loss and hypertension: a systematic review and meta-analysis

“…Accumulation of advanced glycation end products (AGE) with aging leads to increased arterial stiffness and contributes to the development of isolated systolic hypertension 82 , 83 . Excessive intake of animal-derived foods which are rich in fat and AGE may increase the risk of hypertension and other chronic disease 84 – 87 . In general, since individuals who suffer from decreased masticatory function due to tooth loss tend to eat foods that are high in fat 88 – 91 , this may induce AGE accumulation, consequently contribution to increased SBP.…”

The Relationship Between Tooth Loss and Hypertension: a Systematic Review and Meta-analysis

“…Excessive intake of animal-derived foods that are rich in AGE may increase the risk of hypertension and other chronic disease [72][73][74][75] . In general, individuals who suffer from decreased masticatory function due to tooth loss tend to eat foods that are high in fat [76][77][78][79] .…”

The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis

“…Some biomarkers have been identified for diagnosis, prognosis, and response to treatment in SSc-ILD ( 2 ). Other biomarkers were linked to SSc-PAH ( 3 , 4 ),. However, no reliable prospective biomarker has been identified that can predict new onset of SSc-ILD or SSc-PAH in patients with SSc.…”