Circulating miRNAs as Potential Marker for Pulmonary Hypertension

Abstract

MircoRNAs (miRNAs) are small non-coding RNAs that govern the gene expression and, play significant role in the pathogenesis of heart failure. The detection of miRNAs in circulation of pulmonary hypertensive (PH) human subjects remains elusive. In the current study, we determined the pattern of miRNAs of mild-to-severe human PH subjects and, compared them with the control subjects by miRNA array. Blood was obtained using fluoroscopic and waveform guided catheterization from the distal (pulmonary artery) port of the catheter. A total 40 human subjects were included in the study and, the degree of PH was determined by mean pulmonary arterial pressure. Among several miRNAs in the array, we validated 14 miRNAs and, the data were consistent with the array profile. We identified several novel downregulated miRNAs (miR-451, miR-1246) and upregulated miRNAs (miR-23b, miR-130a and miR-191) in the circulation of PH subjects. Our study showed novel set of miRNAs which are dysregulated in PH and, are directly proportional to the degree of PH. These miRNAs may be considered as potential biomarker for early detection of PH.

Translational Advances in the Field of Pulmonary Hypertension.Translating MicroRNA Biology in Pulmonary Hypertension. It Will Take More Than “miR” Words

“…For example, circulating levels of miR-150 (72), miR-26a (73), miR-23a (74), and miR-125a (75) have been reported as reduced in patients with PAH. Dysregulation of entire sets of circulating miRNAs in PAH has also been described (74,76). Other miRNAs with known causative actions in PAH, such as the miR-130/301 family (20) and miR-210 (14), have been found to be elevated in the pulmonary circulation of patients with PH.…”

miRNAs and lncRNAs in vascular injury and remodeling

“…It has been shown that a collection of miRNAs, such as miR-451 and miR-1246, decreased, while several miRNAs, such as miR-23b, miR-130a and miR-191, increased in the plasma of patients with PAH. These studies might have important implications for clinical research aiming to establish whether miRNAs could be used as biomarkers for PAH [57]. However, as the currently available methods used for PAH detection are limited to catheterization performed under X-ray fluoroscopy, extensive work on developing simple and effective detection methods using high specificity and sensitivity plasma markers is needed.…”

Assessment of Operability of Patients With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease

“…Many different pathways are involved in PAH, and multiple biomarkers for PAH have been described, including atrial natriuretic peptide and brain natriuretic peptide (BNP), 28 N-terminal pro-BNP, 29 cardiac troponin T, 30 uric acid, 31 urinary prostaglandin metabolites, 32 endothelial NO synthase (eNOS) and dimethylarginines, 33,34 ET-1 and ET-1:ET3 ratio, 35,36 circulating von Willebrand factor, 37,38 biomarkers of inflammation and oxidative stress such as cytokines (IL-1a, -2, -4, -6, -8, -10 and 12p70, TNF-b, MCP-1 and osteopontin), 39-42 C-reactive protein, 43 50 have also been identified as biomarkers in PAH, with possible implications on outcomes. It is of importance to differentiate markers that indeed reflect right ventricular dysfunction from markers of endothelial dysfunction and finally markers that might predict potential reversibility of the pulmonary vascular lesions; the latter being the one that will discriminate operable vs. inoperable patients.…”

“…53 Micro-RNAs are small, endogenously expressed non-coding RNAs that regulate gene expression at a post-transcriptional level. 50 Micro-RNAs have been implicated in many different settings of cardiovascular remodeling, including blood vessel development, angiogenesis and vascular injury. 54, 55 They have been identified as biomarkers for early diagnosis in acute myocardial infarction and heart failure.…”

“…54, 55 They have been identified as biomarkers for early diagnosis in acute myocardial infarction and heart failure. 56- 60 Wei et al identified a significantly different profile of circulating micro-RNAs in patients with PAH compared to controls, 50 proportional to the degree of PAH. Rhodes et al also showed, more specifically, that downregulation of microRNA-150 is associated with a reduced 2-year survival in patients with established PAH.…”