Benjamin Atchison

Pulmonary hypertension (PH) is a progressive and life-threatening disease characterised by elevated pulmonary arterial pressure, vascular remodelling and right ventricular dysfunction. Emerging evidence implicates circular RNAs (circRNAs) in the regulation of vascular remodelling and inflammation; however, their contribution to PH remains poorly understood. Here, we performed an in silico analysis using a multi-tool circRNA discovery pipeline across three publicly available transcriptomic datasets derived from experimental rat models of PH: H_PRN (PRJNA809145; pulmonary artery tissue from normoxic and hypoxia-induced PH rats; 21% vs. 10% O₂; n = 7), H_GSE (GSE159668; right lung tissue from normoxic and hypoxia-induced PH rats; 21% vs. 10% O₂; n = 6) and M_PRN (PRJNA732522; total lung tissue from control and monocrotaline-induced PH rats; n = 6). CircRNAs were detected in all datasets; however, robust differentially expressed candidates were identified primarily in the hypoxia-exposed pulmonary artery dataset (H_PRN). In this dataset, three circRNAs—circCnot6l, circSmoc1 and circNtrk3—met the differential expression criteria (Benjamini-Hochberg adjusted p-value (FDR q) < 0.05, absolute log₂ fold-change > 1). Downstream network analysis from unpaired samples prioritised circCnot6l and circNtrk3 as potential regulators of circRNA–microRNA (miRNA) and miRNA–messenger RNA axes involving miR-204-5p and miR-205, respectively. The predicted target networks were enriched for genes associated with key PH-related processes, including cell proliferation, adhesion, migration, angiogenesis and vascular development. Collectively, these findings identify circCnot6l and circNtrk3 as promising circRNA candidates involved in hypoxia-induced pulmonary artery remodelling and provide a foundation for future experimental studies investigating circRNA-mediated mechanisms underlying PH pathogenesis.

Pulmonary hypertension (PH) is a progressive and life-threatening disease characterised by elevated pulmonary arterial pressure, vascular remodelling and right ventricular dysfunction. Emerging evidence implicates circular RNAs (circRNAs) in the regulation of vascular remodelling and inflammation; however, their contribution to PH remains poorly understood. Here, we performed an in silico analysis using a multi-tool circRNA discovery pipeline across three publicly available transcriptomic datasets derived from experimental rat models of PH: H_PRN (PRJNA809145; pulmonary artery tissue from normoxic and hypoxia-induced PH rats; 21% vs 10% O2; n=7), H_GSE (GSE159668; right lung tissue from normoxic and hypoxia-induced PH rats; 21% vs 10% O2; n=6) and M_PRN (PRJNA732522; total lung tissue from control and monocrotaline-induced PH rats; n=6). CircRNAs were detected in all datasets; however, robust differentially expressed candidates were identified primarily in the hypoxia-exposed pulmonary artery dataset (H_PRN). In this dataset, three circRNAs—circCnot6l, circSmoc1 and circNtrk3—met the differential expression criteria (FDR q < 0.05, absolute log₂ fold change > 1). Downstream network analysis prioritised circCnot6l and circNtrk3 as potential regulators of circRNA–miRNA–mRNA axes involving miR-204-5p and miR-205, respectively. The predicted target networks were enriched for genes associated with key PH-related processes, including cell proliferation, adhesion, migration, angiogenesis and vascular development. Collectively, these findings identify circCnot6l and circNtrk3 as promising circRNA candidates involved in hypoxia-induced pulmonary artery remodelling and provide a foundation for future experimental studies investigating circRNA-mediated mechanisms underlying PH pathogenesis.

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1–2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16%-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1%-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.