Fina Lovren
Senior Research Associate
PhD and PharmD
416-864-6060 x77626/77457
lovrenf@smh.ca
Dr. Fina Lovren's research includes studies of angiotensin-converting enzyme 2 (ACE2) on endothelial cell regulation. Endothelium plays a central role in the maintenance of vascular homeostasis, and impaired endothelial function contributes to the development and progression of diverse diseases. One of the main effectors of endothelial dysfunction is angiotensin-II (AngII), and pharmacological approaches to limit AngII bioactivity remain the cornerstone of current cardiovascular therapeutics. Recently, ACE2 has been identified as a critical negative modulator of AngII bioactivity, which serves to counterbalance the effects of ACE in determining net tissue AngII levels. Although ACE2 is highly expressed within the endothelium, the functional significance of ACE2 at the cellular level is unknown. Additionally, its localization in vascular endothelium suggests that ACE2 may have a role in the control of atherosclerosis. Therefore, in our studies we will evaluate the role of ACE2 on the endothelial function and progression of atherosclerosis by employing molecular, gene-deficient and over-expression strategies. We hypothesize that in endothelial cells ACE2 will stimulate angiogenesis, prevent apoptosis and modulate Ang II-induced upregulation of adhesion molecules and chemokines. Secondly, we hypothesize that treatment with recombinant adenovirus ACE2 will significantly attenuate atherosclerosis in ApoE-/- knockout mice, resulting in favorable changes of atherosclerotic genes.
Singh KK, Shukla PC, Quan A, Desjardins JF, Lovren F, Pan Y, Garg V, Gosal S, Garg A, Szmitko PE, Schneider MD, Parker TG, Stanford WL, Leong-Poi H, Teoh H, Al-Omran M, Verma S.
BRCA2 Protein Deficiency Exaggerates Doxorubicin-induced Cardiomyocyte Apoptosis and Cardiac Failure.
J Biol Chem. 2012 Feb 24;287(9):6604-14
Yanagawa B, Lovren F, Pan Y, Garg V, Quan A, Tang G, Singh KK, Shukla PC, Kalra NP, Peterson MD, Verma S.
miRNA-141 is a novel regulator of BMP-2-mediated calcification in aortic stenosis.
J Thorac Cardiovasc Surg. 2012 Feb 13.
Teoh H, Quan A, Creighton AK, Annie Bang KW, Singh KK, Shukla PC, Gupta N, Pan Y, Lovren F, Leong-Poi H, Al-Omran M, Verma S.
BRCA1 gene therapy reduces systemic inflammatory response and multiple organ failure and improves survival in experimental sepsis.
Gene Ther. 2012 Jan 19. doi: 10.1038/gt.2011.214.
Shukla PC, Singh KK, Quan A, Al-Omran M, Teoh H, Lovren F, Cao L, Rovira II, Pan Y, Brezden-Masley C, Yanagawa B, Gupta A, Deng CX, Coles JG, Leong-Poi H, Stanford WL, Parker TG, Schneider MD, Finkel T, Verma S.
BRCA1 is an essential regulator of heart function and survival following myocardial infarction.
Nat Commun. 2011 Dec 20;2:593.
Singh KK, Shukla PC, Quan A, Lovren F, Pan Y, Wolfstadt JI, Gupta M, Al-Omran M, Leong-Poi H, Teoh H, Verma S.
Herceptin, a recombinant humanized anti-ERBB2 monoclonal antibody, induces cardiomyocyte death.
Biochem Biophys Res Commun. 2011 Jul 29;411(2):421-6.
Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, Al-Omran M, Teoh H, Verma S.
Adropin is a novel regulator of endothelial function
Circulation. 2010 Sep 14;122(11 Suppl):S185-92.
Lovren F, Pan Y, Quan A, Szmitko PE, Singh KK, Shukla PC, Gupta M, Chan L, Al-Omran M, Teoh H, Verma S.
Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages.
Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H656-63.
Lovren F, Pan Y, Shukla PC, Quan A, Teoh H, Szmitko PE, Peterson MD, Gupta M, Al-Omran M, Verma S.
Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis.
Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1440-9.
Lovren F, Pan Y, Quan A, Teoh H, Wang G, Shukla PC, Levitt KS, Oudit GY, Al-Omran M, Stewart DJ, Slutsky AS, Peterson MD, Backx PH, Penninger JM, Verma S.
Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis.
Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1377-84.