Research & Publications
My clinical research is focused on the design, reporting and regulatory documentations for interventional cardiovascular device trials, including First-in-Human, CE Mark, IDE/IND Phase III and IV trials and post marketing studies in the US and worldwide.
In the laboratory my research had been focused on growth regulatory mechanisms generated by the endothelium-to-cardiomyocytes communication through the endothelium-released nitric oxide, Gi /Gq protein signaling and microRNAs.
Specialized Terms: Ischemic Heart Disease; Medical Devices; Clinical Trial; Endothelium-Cardiomyocytes Communication; Myocardial Hypertrophy; Nitric Oxide; Gi/Gq Signaling; microRNAs.
Extensive Research Description
Dr. Tirziu has made substantial contributions to scientifically sound clinical research documents, regulatory documents (clinical trial protocols and study reports) and meta-analyses on several novel cardiovascular devices and cerebral embolic protection devices during transcatheter heart procedures.
Findings from laboratory showed that the induction of myocardial angiogenesis promotes cardiomyocyte growth and myocardial hypertrophy through a nitric oxide (NO)-dependent mechanism that leads to the degradation of regulator of G protein signaling type 4 (RGS4), de-repression of the Gβγ/PI3Kγ/Akt/mTORC1 pathway and up-regulation of miR-182 and miR-146b expression in cardiomyocytes. The hypertrophy observed in this model is physiological and preserves contractile function. The molecular and functional differences between pathological and physiological hypertrophy are not fully understood and an important unanswered question is whether the mechanisms responsible for the physiological hypertrophic response can be exploited to prevent pathological hypertrophy and heart failure in patients with left ventricle (LV) pressure overload. Therefore we aimed to determine:
(1) The role of the Arg/N-end rule pathway in RGS4 degradation and activation of hypertrophic signaling through Gq and Gi proteins.
(2) The differential effect of angiogenesis NO-driven physiological hypertrophy versus G protein coupled receptor (GPCR)-driven pathological hypertrophy on miR-182 or miR-146b expression in cardiomyocytes.
(3) The functional significance of endothelium-driven myocardial hypertrophy and whether it is beneficial during pathological stress of pressure overload or myocardial infarction.
(4) The cardio-protective potential of miR-182 or miR-146b during the pathological stress of pressure overload.
Cardiovascular Diseases; Cell Communication; Endothelium, Vascular; Heart Diseases; Heart Failure; Clinical Trial; MicroRNAs; Endothelium-Dependent Relaxing Factors; Gene Regulatory Networks; Publication Characteristics
- Cardiac Hypertrophy: Signaling and Cellular CrosstalkTirziu D., Cardiac Hypertrophy: Signaling and Cellular Crosstalk, 2018. In: Vasan R., Sawyer, D.(eds.) The Encyclopedia of Cardiovascular Research and Medicine, vol., pp. 434-450. Oxford: Elsevier