ABSTRACT
The onset and progression of pulmonary arterial hypertension (PAH), a malignant disease, are associated with environmental and epigenetic factors. Recent advancements in transcriptomics and proteomics technology have provided new insights into PAH and identified novel gene targets involved in the development of the disease. Transcriptomic analysis has led to the discovery of possible novel pathways, such as miR-483 targeting several PAH-related genes and a mechanistic link between the increase in HERV-K mRNA and protein. Proteomic analysis has revealed crucial details, including the loss of SIRT3 activity and the significance of the CLIC4/Arf6 pathway in PAH pathogenesis. Gene profiles and protein interaction networks of PAH have been analyzed, clarifying the roles of differentially expressed genes or proteins in the occurrence and development of PAH. This article discusses these recent advances.
Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/pathology , Proteomics , Transcriptome/genetics , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/metabolism , Gene Expression Profiling , Chloride Channels/genetics , Chloride Channels/metabolismABSTRACT
Pulmonary vascular remodeling was shown to lead to pulmonary arterial hypertension (PAH), further trigger excessive apoptosis of cardiomyocytes, and ultimately cause right ventricular failure (RVF), which involves the activation of Rho A/ROCK signaling pathway. Betaine has been found efficacious for attenuating PAH through its anti-inflammatory effects in our previous research while its effects on RVF due to PAH remains inconclusive. Thus, we attempted to elucidate the protective effects of betaine on PAH, RVF due to PAH as well as the potential mechanisms. To this end, male Sprague Dawley rats received a single subcutaneous injection of monocrotaline (50 mg/kg) to imitate PAH and RVF, and subsequently oral administration of betaine (100, 200, and 400 mg/kg/day). Betaine treatment improved the hemodynamics and histomorphological parameters and echocardiographic changes. Moreover, betaine also alleviated the pulmonary vascular remodeling and cardiomyocyte apoptosis. The mechanisms study revealed that administration of betaine significantly increased the expression of Rho A, ROCK1, and ROCK2. Furthermore, betaine alleviated the changes of its downstream molecules P53, Bcl-2, Bax, phosphorylated MYPT1 (p-MYPT1), total MYPT1 (t-MYPT1), p27kip1, and Cleaved Caspase-3. According to what we observed, this study indicated that betaine treatment could protect RVF due to PAH, which may be achieved through an altered Rho A/ROCK signaling pathway.
Subject(s)
Betaine/pharmacology , Heart Failure/drug therapy , Pulmonary Arterial Hypertension , rho GTP-Binding Proteins/metabolism , rho-Associated Kinases/metabolism , Actins/metabolism , Administration, Oral , Animals , Apoptosis/drug effects , Arterioles/drug effects , Betaine/administration & dosage , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/pharmacology , Disease Models, Animal , Electrocardiography/drug effects , Heart Failure/chemically induced , Heart Failure/etiology , Heart Failure/pathology , Heart Ventricles/drug effects , Heart Ventricles/pathology , Male , Monocrotaline/toxicity , Proliferating Cell Nuclear Antigen/metabolism , Pulmonary Arterial Hypertension/chemically induced , Pulmonary Arterial Hypertension/complications , Pulmonary Arterial Hypertension/pathology , Pulmonary Artery/drug effects , Rats, Sprague-Dawley , Signal Transduction/drug effects , Vascular Remodeling/drug effectsABSTRACT
A PIDA-promoted cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) and aryl ketones for efficient synthesis of N-alkoxyphthalimide products in moderate to good yields has been described. This methodology is distinguished by catalyst-free conditions, readily available starting materials, wide substrate scope and operational simplicity. In addition, a gram-scale reaction and synthetic transformation of the product into synthetically useful intermediates has been demonstrated.
