Reduced endothelial-pericyte interactions are linked to progressive small vessel loss in pulmonary arterial hypertension (PAH), but the molecular mechanisms underlying this disease remain poorly understood. To identify relevant gene candidates associated with aberrant pericyte behavior, we performed a transcriptome analysis of patient-derived donor control and PAH lung pericytes followed by functional genomics analysis. Compared with donor control cells, PAH pericytes had significant enrichment of genes involved in various metabolic processes, the top hit being PDK4, a gene coding for an enzyme that suppresses mitochondrial activity in favor of glycolysis. Given reports that link reduced mitochondrial activity with increased PAH cell proliferation, we hypothesized that increased PDK4 is associated with PAH pericyte hyperproliferation and reduced endothelial-pericyte interactions. We found that PDK4 gene and protein expression was significantly elevated in PAH pericytes and correlated with reduced mitochondrial metabolism, higher rates of glycolysis, and hyperproliferation. Importantly, reducing PDK4 levels restored mitochondrial metabolism, reduced cell proliferation, and improved endothelial-pericyte interactions. To our knowledge, this is the first study that documents significant differences in gene expression between human donor control and PAH lung pericytes and the link between mitochondrial dysfunction and aberrant endothelial-pericyte interactions in PAH. Comprehensive characterization of these candidate genes could provide novel therapeutic targets to improve endothelial-pericyte interactions and prevent small vessel loss in PAH.

Pulmonary hypertensive crisis is an important cause of morbidity and mortality in patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD) who require cardiac surgery. At present, prevention and management of perioperative pulmonary hypertensive crisis is aimed at optimizing cardiopulmonary interactions by targeting prostacyclin, endothelin, and nitric oxide signaling pathways within the pulmonary circulation with various pharmacological agents. This review is aimed at familiarizing the practitioner with the current pharmacological treatment for dealing with perioperative pulmonary hypertensive crisis in PAH-CHD patients. Given the life-threatening complications associated with pulmonary hypertensive crisis, proper perioperative planning can help anticipate cardiopulmonary complications and optimize surgical outcomes in this patient population.

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Pulmonary arterial hypertension (PAH) is a devastating disease associated with progressive elevation in pulmonary pressures that eventually leads to chronic right heart failure and death. At present, agents with vasodilatory properties are being used to palliate the symptoms associated with PAH but there is a need for therapies that can prevent or even reverse established disease. Several lines of evidence have suggested that tyrosine kinase inhibitors like imatinib may have a role in reducing progression and improving outcomes in these patients, but their side effect profile is unclear. We present a case of a 55-year-old female with PAH secondary to connective tissue disease treated with triple PAH specific therapy and compassionate-use imatinib who developed a massive right pleural effusion. Despite multiple therapeutic thoracentesis and aggressive diuresis, the pleural effusion continued to re-accumulate necessitating chest tube placement. Resolution of the pleural effusion was finally achieved after imatinib was held, arguing that the patient's presentation likely was a drug-related event. We believe that our case highlights a serious adverse reaction to imatinib therapy and stresses the need for more studies to evaluate the safety profile of this medication in patients with PAH.