From Clinic To Basic Reserch: Investigation Of Diagnostic Criteria Of HFpEF And Study Of Adenovirus Mediated Relaxin-2Gene Therapy And Potential Mechanism

Aims: There are no unified criteria for diagnosing heart failure with preserved ejectionfraction (HFpEF). The aim was to evaluate the present main diagnostic criteria and todiscover which parameters and strategies are more valuable.Methods: Echocardiographic data and plasma NT-proBNP levels were assessed in aderivation cohort and a validation cohort with normal controls, patients with hypertensiveheart disease without heart failure and with HFpEF.Results: In the derivation cohort, the ratio of early mitral inflow velocity to tissue Dopplervelocity at lateral mitral annulus (lateral E/e’≥12), left atrial volume index (LAVI≥34ml/m2) and the difference between duration of reversed pulmonary vein atrial systole flowand duration of mitral A wave flow (Ard－Ad＞30ms) had the greatest diagnostic valueamong all the single parameters. A brief strategy that consisted of these3parameters: when⑴lateral E/e’≥12;⑵12＞lateral E/e’≥8, either LAVI≥34ml/m2or Ard－Ad＞30msare required for identifying diastolic dysfunction in HFpEF, provided a great diagnosticaccuracy with a sensitivity of77%and specificity of81%. And these observations were confirmed by the validation cohort.Conclusion: Echocardiographic parameters including lateral E/e’, LAVI and Ard－Ad havethe greatest value in diagnosing HFpEF. The brief strategy that consisted of these3parameters has great diagnostic value and is simple to be applied in clinic practice. Aims: The aim of the present study is to investigate effect of adenovirus mediated relaxin-2gene therapy on cardiac function of pressure overloaded rat induced by trans-aorticconstrictionMethods:1. construction of adenoviral vector with relaxin-2gene and control adenoviralvector with GFP.2. Pressure overload of SD rats was induced by trans-aortic constriction.4weeks later, diastolic dysfunction was demonstrated by echocardiographic parameters suchas E/A and tissue Doppler Image e’/a’.3. Then adenoviral vector with relaxin gene(Ad-GFP-RLX2) and with GFP (Ad-GFP) was injected into the left ventricularmyocardium, respectively. Two weeks after injection, echocardiography and catheterizationwas performed to evaluate the diastolic function.Results: Improvement of E/A (1.86±0.24vs1.52±0.28,1.54±0.21, p<0.05), tissueDoppler Image e’/a’(1.24±0.49vs0.42±0.41,0.46±0.37, p<0.05) and–dp/dtmax(-5956±1104vs-4864±1171,-4583±1123, p<0.05) was observed in pessureoverloaded rats with relaxin gene therapy, compared to normal control and Ad-GFP controlgroups. However, systolic parameters such as left ventricular ejection fraction andfractional shortening were not significantly different.Conclusions: Intramyocardial delivery of adenovirus mediated relaxin improves diastolicfunction of SD rats with pressure overload induced by trans-aortic constriction Aims: The aim of the present study is to investigate the potential mechanism ofadenovirus mediated relaxin-2gene therapy on ameliorating diastolic dysfunction of SD ratwith diasotlic heart failure induced by trans-aortic constrictionMethods: After performing echocardiography and invasive catheteraization, harvest theheart of4groups of rats including: normal control (CON), control of rat2with diastolicheart failure (DHF), rats with DHF and Ad-GFP injection, and rats with DHF andAd-GFP-RLX2injection. Evaluation of the protein levels of AKT phospho-Ser473andphospho-Thr308, and the protein levels of phospholamban phospho-Ser16andphospho-Thr17by Western Blotting.Results: adenovirus mediated relaxin gene therapy activated AKT singnaling pathway byenhancing the phosphorylation of both phospho-Ser473and phospho-Thr308of AKT,and then enhancing the phosphorylation level of phospholamban at Ser16and Thr17.Conclusions: Intramyocardial delivery of adenovirus mediated relaxin improves diastolicfunction of rats with diastolic heart failure by enhancing phosphorylation ofphospholamban through activating AKT signaling pathway.