Mitochondria as a primary determinant of angiogenic modality in pulmonary arterial hypertension.

Impaired pulmonary angiogenesis plays a pivotal role in the progression of pulmonary arterial hypertension (PAH) and patient mortality, yet the molecular mechanisms driving this process remain enigmatic. Our study uncovered a striking connection between mitochondrial dysfunction (MD), caused by a humanized mutation in the NFU1 gene, and severely disrupted pulmonary angiogenesis in adult lungs. Restoring the bioavailability of the NFU1 downstream target, lipoic acid (LA), alleviated MD and angiogenic deficiency and rescued the progressive PAH phenotype in the NFU1G206C model.

Circulating free heme induces cytokine storm and pulmonary hypertension through the MKK3/p38 axis.

Hemolysis is associated with pulmonary hypertension (PH), but the direct contribution of circulating free heme to the PH pathogenesis remains unclear. Here, we show that the elevated levels of circulating free heme are sufficient to induce PH and inflammatory response in mice and confirm the critical role of mitogen-activated protein kinase kinase-3 (MKK3)-mediated pathway in free heme signaling. Following the continuous infusion of heme for 2 wk, wild-type (WT) but not MKK3 knockout (KO) mice develop PH, as evidenced by a significantly elevated right ventricular (RV) systolic pressure, RV hypertrophy, and pulmonary vascular remodeling.

Deciphering the Complexities of Pulmonary Hypertension: The Emergent Role of Single-Cell Omics.

Expanding upon the critical advancements brought forth by single-cell omics in pulmonary hypertension (PH) research, this review delves deep into how these technologies have been piloted in a new era of understanding this complex disease. By leveraging the power of single cell transcriptomics (scRNA-seq), researchers can now dissect the complicated cellular ecosystem of the lungs, examining the key players such as endothelial cells, smooth muscle cells, pericytes, and immune cells, and their unique roles in the pathogenesis of PH. This more granular view is beyond the limitations of traditional bulk analysis, allowing for the identification of novel therapeutic targets previously obscured in the aggregated data.

Occurrence of Arbuscular Mycorrhizal Herbs Decreases Selectively in Communities Dominated by Invasive Tree Acer negundo.

We tested whether one of the consequences predicted for alien plant invasion by the mutualism disruption hypothesis was true in the case of the ash-leaved maple Acer negundo L. The study aimed to determine whether the occurrences of mycorrhizal and nonmycorrhizal herbs varied similarly or differently in communities with varying degrees of A. negundo dominance.