Experimental animal models of pulmonary hypertension:Development and challenges

Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.

Implication of proliferation gene biomarkers in pulmonary hypertension

Objective/Background:Proliferation is a widely recognized trigger for pulmonary hypertension(PH),a life-threatening,progressive disorder of pulmonary blood vessels.This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis.Methods:Human pulmonary arterial smooth muscle cells(hPASMCs)were cultured in the presence or absence of human recombinant platelet derived growth factor(rhPDGF)-BB.Cells were collected for metabolomics or transcriptomics study.Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database.Results:90 metabolites(VIP score>1,fold change>2 or<0.5 and p<.05)and 2701 unique metabolism associated genes(MAGs)were identified in rhPDGF-BB treated hPASMCs compared to control cells.In addition,1151 differentially expressed genes(313 upregulated and 838 downregulated)were identified in rhPDGF-BB treated hPASMCs compared to control cells(fold change>2 or<0.5 and p<.05).152 differentially expressed MAGs were then determined,out of which 9 hub genes(IL6,CXCL8,CCL2,CXCR4,CCND1,PLAUR,PLAU,HBEGF and F3)were defined as core proliferation associated hub genes in protein proten interaction analysis.In addition,the hub gene-based LASSO model can predict the occurrence of PH(AUC=0.88).The expression of CXCR4,as one of the hub genes,was positively correlated to immune cell infiltrates.Conclusion:Our findings revealed some key proliferation associated genes in PH,which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.

Building a modern six-dimensional biobank fosters the future of precision medicine

In 2001, Dr. Zhi-Cheng Jing encountered a pulmonary arterial hypertension (PAH) patient from a large pedigree. Dr. Jing collected the clinical information and blood samples from this pedigree and was the first to report the pedigree of familial PAH in China [1]. In2004, this pedigree was confirmed to carry a mutation in BMPR2(Arg491Trp), which was the first evidence of pathogenicity of BMPR2 mutation in the Chinese population [2].

Inflammation and cardiovascular diseases

Despite great advances in the diagnosis and therapy of cardiovascular diseases(CVDs)over the last few decades,they remain the leading causes of morbidity and mortality worldwide and have emerged as the leading causes of death in China.1 This is partly due to the fact that the exact pathogenic mechanisms remain poorly understood in most cases,which significantly limits the effectiveness of therapy.Thus,identification of the key mechanisms that regulate cardiovascular function and the novel preventable risk factors of CVDs is urgently needed.

Standard Operation Procedure of Percutaneous Endomyocardial Biopsy in Peking Union Medical College Hospital

Percutaneous endomyocardial biopsy (EMB) is a technique that biopsy samples are obtained using bioptome through peripheral blood vessel. This technique has been used and refined more than 50 years in clinical application. Now EMB has become an important diagnostic tool in the diagnosis of myocarditis and cardiomyopathy. Department of cardiology, Peking Union Medical College Hospital (PUMCH) has performed more than 500 cases of EMB and accumulated abundant practical experience. The clinical practice guideline of percutaneous EMB in PUMCH was also established, including indications, contradictions, operation key points, sample handling and processing, post-procedure monitoring, and treatment strategy for potential complications, etc. Due to the limitation of EMB, cardiologists should collaborate with experts in echocardiography, cardiac magnetic resonance and cardiac pathology to avoid missed diagnosis and misdiagnosis. Cardiologists should pay more attention to the value of EMB and actively perform EMB to improve the diagnosis level for myocarditis and cardiomyopathy in China.