Eicosapentaenoic acid ameliorates pulmonary hypertension via inhibition of tyrosine kinase Fyn.

Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by pulmonary arterial vasoconstriction and remodeling. Src family tyrosine kinases, including Fyn, play critical roles in vascular remodeling via the inhibition of STAT3 signaling. EPA is known to inhibit Fyn kinase activity. This study investigated the therapeutic potential and underlying mechanisms of EPA and its metabolite, resolvin E1 (RvE1), to treat PAH using monocrotaline-induced PAH model rats (MCT-PAH), human pulmonary artery endothelial cells (HPAECs), and human pulmonary artery smooth muscle cells (HPASMCs). Administration of EPA 1 and 2 weeks after MCT injection both ameliorated right ventricular hypertrophy, remodeling and dysfunction, and medial wall thickening of the pulmonary arteries and prolonged survival in MCT-PAH rats. EPA attenuated the enhanced contractile response to 5-hydroxytryptamine in isolated pulmonary arteries of MCT-PAH rats. Mechanistically, the treatment with EPA and RvE1 or the introduction of dominant-negative Fyn prevented TGF-ß2-induced endothelial-to-mesenchymal transition and IL-6-induced phosphorylation of STAT3 in cultured HPAECs. EPA and RvE1 suppressed Src family kinases' activity as evaluated by their phosphorylation status in cultured HPAECs and HPASMCs. EPA and RvE1 suppressed vasocontraction of rat and human PA. Furthermore, EPA and RvE1 inhibited the enhanced proliferation and activity of Src family kinases in HPASMCs derived from patients with idiopathic PAH. EPA ameliorated PAH's pathophysiology by mitigating vascular remodeling and vasoconstriction, probably inhibiting Src family kinases, especially Fyn. Thus, EPA is considered a potent therapeutic agent for the treatment of PAH.

Pulmonary hypertension: a review of current clinical practice / 中华心血管病杂志

This short review illustrates current epidemiology, diagnosis and treatment of pulmonary hypertension. In the first part, classification, definition and prevalence of pulmonary hypertension (PH) are explained. According to recent reports, overall PH prevalence was 0.3% to 6.0% with left heart disease occupying the most proportion, followed by pulmonary disease, pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) constituting far less proportion of 10 to 50 per 1 million people. In diagnosis, flow of diagnosis of PH, differential diagnosis of PH and how to determine the severity of PH are explained including recent development of magnetic resonance imaging (MRI) and gene abnormality study on BMPRII. In treatment, newly-developed pulmonary vasodilators are shown as well as how to combine them in PAH, and in CTEPH treatment the drugs, operation and catheter therapy including our experience are demonstrated.

Current practice for pulmonary hypertension / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the current practice of pulmonary hypertension including current epidemiology, diagnosis and treatment.</p><p><b>DATA SOURCES</b>The review was based on data obtained from the published articles and guidelines.</p><p><b>STUDY SELECTION</b>Articles with high level of evidence or current best evidence in each issue were selected to be reviewed.</p><p><b>RESULTS</b>Overall prevalence of pulmonary hypertension was 0.3% to 6% with left heart disease occupying the most proportion, followed by pulmonary disease, pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. In diagnosis, a flow diagram of diagnosis of pulmonary hypertension, differential diagnosis of pulmonary hypertension and how to determine the severity of pulmonary hypertension are explained including recent development of magnetic resonance imaging and gene abnormality study on bone morphogenetic protein receptor II. In treatment, newly-developed pulmonary vasodilators and the way to use them are shown to treat pulmonary hypertension.</p><p><b>CONCLUSION</b>Safer and more effective treatment algorithm and basic researches and clinical trials are warranted to be explored.</p>

Coronary Artery Bypass Grafting in the Presence of Atherosclerotic Lesions in the Ascending Aorta / 日本心臓血管外科学会雑誌

The results and surgical techniques were studied in 59 patients who had atherosclerotic lesions in the ascending aorta. Arterial grafting (AG) and sequential grafting for coronary artery bypass grafting (CABG) was used in as many as possible cases and the number of distal anastomoses with AG was 1.3/patient (internal thoracic artery (ITA), 56 anastomoses for 50 patients; gastroepiploic artery (GEA), 17; and inferior epigastric artery, 3). Calcification in the ascending aorta was noted in 26 patients and arterial cannulation was performed via the right axillary artery in 4 patients. Saphenous vein grafts were used for 51 patients and 30 of them required aortic reconstruction for proximal anastomosis. There were 2 hospital deaths (non-cardiac) and no neurological complications. It is difficult to perform CABG in the presence of atherosclerosis in the ascending aorta. However, the right axillary artery cannulation as the site of arterial cannulation and the use of sequential grafting, using ITA and GEA as the pedicled arterial conduits are useful to accomplish CABG in such patients. Neurological complication seems to be manufactured at a minimal level by cautious operative techniques.