Fina Lovren
Title
: Research Associate
Degree(s) : PhD and PharmD
Phone #s : 416-864-6060 x3581/x3582 Fax # : 416-864-5497
ACE2: Novel regulator of endothelial function and atherosclerosis My area of 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.
Select Publications :
L. Ko, A. Maitland, P. W. Fedak, A. s. Dumont, M. Badiwala, F. Lovren, C. R. Triggle, T. J. Anderson, V. Rao, S. Verma (2002). Endothelin blockade potentiates endothelial protective effects of ACE inhibitors in saphenous vein.
Ann. Thorac. Surg. 73, 1185-8 J. C. Wanstall, T. K. Jeffery, A. Gambino, F. Lovren, C. R. Triggle (2001). Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparition with acetylcholine, nitric oxide and nitroxyl ion.
Br. J. Pharmacol. 134, 463-472 S. Verma, F. Lovren, A. Dumont, K. Mather, A. Maitland, T. Kieser, W. Kidd, J. McNeill, D. Stewart C.Triggle & T. Anderson (2001) Endothelin receptor blockade improves endothelial function in human internal mammary arteries.
Cardiovascular Research 49, 146-151 S. Verma, F. Lovren, A. Dumont, K. Mather, A. Maitland, T. Kieser, C. R. Triggle, T. J. Anderson (2000) Tetrahydrobiopterin improves endothelial function in human saphenous veins: a novel mechanism. J. Thorac. Cardiovasc. Surg. 120, 668-671 M. N. Muscara, W. McKnight, F. Lovren, C. R. Triggle, G. Cirino, and J. L. Wallace (2000) Anti-hypertensive properties of nitric oxide-releasing Naproxen derivative in 2-kidney, 1-clip rats. Am. J.
Physiol ‑ Heart 279, H528-535 F. Lovren, C.R.Triggle (2000) Nitric oxide and sodium nitroprusside -induced relaxation of the human umbilical artery.
Br. J. Pharmacol. 131, 521-529 F. Lovren, X.F. Li, J. Lytton & C.R. Triggle (1999) Functional characterization and m-RNA expression of 5-HT receptors mediating contraction in human umbilical artery.
Br. J. Pharmacol. 127, 1247-1255. F. Lovren & C.R. Triggle (1998) Involvement of nitrosothiols, nitric oxide and voltage-gated K+ channels in photorelaxation of vascular smooth muscle. Eu. J. Pharmacol. 347, 215-221.
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