Metallomics in pulmonary arterial hypertension patients

Abstract

Pulmonary arterial hypertension (PAH) prevalence is increasing worldwide, and the prognosis is poor with 5‐year survival < 50% in high risk patients. The relationship between metal exposure/essential metal dyshomeostasis and PAH/right ventricular dysfunction is less investigated. The aim of this study is to investigate vegetable consumptions and metal levels between PAH patients and controls. This was a prospective, single center pilot study. Questionnaires were completed by all study subjects (20 PAH patients and 10 healthy controls) on smoking, metal exposure risks, metal supplements, and vegetable consumptions. Blood and urine samples were collected to measure 25 metal levels in blood, plasma, and urine using an X Series II quadrupole inductively coupled plasma mass spectrometry. Statistical analysis was conducted using SAS 9.5 and results with p value < 0.05 were considered significant. Vegetables consumptions (broccoli risk ratio [RR] = 0.4, CI = (0.2, 0.9)], cabbage [RR = 0.2, CI = (0.1, 0.8)], and brussel sprouts [RR = 0.2, CI = (0.1, 0.5)]) are associated with less risks of PAH. In the plasma samples, silver ( p < 0.001), and copper ( p = 0.002) levels were significantly higher in PAH patients. There was significant positive correlation between cardiac output and cardiac index with plasma levels of silver ( r = 0.665, p = 0.001 and r = 0.678 p = 0.001), respectively. There was significant correlation between mixed venous saturation, 6‐min walk distance, and last BNP with plasma levels of chromium ( r = −0.520, p = 0.022; r = −0.55, p = 0.014; r = 0.463, p = 0.039), respectively. In conclusion, there are significant differences between PAH and control groups in terms of vegetable consumptions and metal concentrations. Silver and chromium levels are correlated with clinical indicators of PAH severities.

Real-Time Exposure to 3D-Printing Emissions Elicits Metabolic and Pro-Inflammatory Responses in Human Airway Epithelial Cells

“…Prior studies also demonstrated that in vivo exposure to the thermo-oxidative degradation of ABS caused a decrease in tissue GSH level [ 87 , 88 ]. Furthermore, exposure to pollution containing Cu can also lead to GSH oxidation and depletion [ 51 , 89 ] and elevation of pro-inflammatory cytokines [ 48 , 50 , 90 ], and cause pulmonary inflammation and hypertension [ 91 ], resulting in serious respiratory diseases including COPD and pneumonia mortality [ 92 ]. Dysregulated cellular redox homeostasis is often associated with increased levels of cytokines.…”

Potential Roles of Metals in the Pathogenesis of Pulmonary and Systemic Hypertension

“…Although there was no direct evidence for the association of exposure to multiple metals with PH, there was a strong association of antimony with PAH and its associated RV pathogenesis 86 . Therefore, investigation for the potential role of metal exposure in the pathogenesis of PH, exposure to mixed metals should be considered for the epidemiological and preclinical studies 56 .…”

“…There was significant positive correlation between cardiac output and cardiac index with plasma levels of silver. There was significant correlation between mixed venous saturation, 6-min walk distance, and last B-type natriuretic peptide with plasma levels of chromium [56]. Furthermore, antimony (Sb) levels correlated with PAH severity [86].…”

“…Therefore, the mitochondrial effects by metals have been considered as the major pathogenic mechanisms for several diseases [52]. However, whether metals-mediated mitochondrial damage occurs in pulmonary arteries and plays any role in the pathogenesis of PH remains largely unknown [7,[54][55][56]. Therefore, the aim for this review is to assess the evidence surrounding essential and non-essential metals, mitochondrial dysfunction, and the subsequent ROS/RNS production in PH.…”

Wastewater-based epidemiology for comprehensive communitywide exposome surveillance: A gradient of metals exposure

“…Chronic exposure to environmental pollutants is recognized as even more important than individual genetic predisposition in causing common chronic diseases (Bhatnagar, 2006; Lamas et al, 2023; Vineis et al, 2020). However, clinically relevant toxicity is much less prevalent, and when occurring may present with non-specific symptoms, resulting in a large differential for clinicians to consider (El-Kersh et al, 2022; El-Kersh et al, 2023; Tan et al, 2023).…”