Frank J. Giordano, M.D. Assistant Professor of Medicine (Cardiovascular Medicine) Director, Cardiovascular Gene Therapy Program Member, Molecular Cardiology Program, BCMM

B.S., University of Illinois, 1980; M.D. Loyola University, 1986; Residency Training, Loyola University, 1986-1989; Chief Resident, Loyola University, 1989-1990; Clinical Cardiology Fellowship, University of California, San Diego (UCSD), 1990-1992; Molecular Biology Fellowship, UCSD, 1992-1994; Interventional Cardiology Fellowship, UCSD, 1994-1995; Assistant Professor of Medicine, UCSD, 1995-1998; Joined Yale Faculty 1998

Mechanisms of Myocardial Angiogenesis;
Development of Therapeutic Cardiovascular
Gene Delivery Strategies

Vasculogenesis (the de novo development of new blood vessels) and angiogenesis (the growth of new blood vessels from a pre-existing vasculature) are inter-related processes that are absolutely essential to viable embryonic development. Angiogenesis, furthermore, plays a critical role in a variety of physiologic and pathophysiologic processes in the adult. Recently, therapeutic stimulation of angiogenesis has been the focus of several clinical trials targeting treatment of severe coronary artery and peripheral vascular disease. Conversely, inhibition of angiogenesis is being vigorously explored as a new weapon against cancer. Despite these attempts to modulate angiogenesis in the clinical setting, the molecular events controlling the angiogenic process are incompletely understood.

We have been studying myocardial angiogenesis at three different levels; at the molecular level in transgenic and knock-out mice, at the pre-clincal level testing the ability of gene delivery and growth factor administration to ameliorate myocardial ischemia in animal models, and the clinical level administering angiogenic factors to patients with severe coronary disease. We are currently investigating the effects of deleting the genes for Vascular Endothelial Growth Factor (VEGF) and the Hypoxia Inducible Factor (HIF-1 a) in the hearts of genetically engineered mice. Targeting deletion of these genes only to the heart will allow us to determine the specific role of these genes in cardiac development, post-natal coronary maturation, and the angiogenic response of the heart to cardiac hypertrophy and ischemic myocardial injury. We are also testing the ability of other growth factors to influence myocardial angiogenesis and potentially effect post-infarction ventricular remodeling.

The great promise of gene therapy has largely been unfulfilled, in part because of significant technical issues of limited gene delivery efficiency, limited duration of gene expression and inflammatory responses to vectors or gene products. We are working in the gene therapy program to develop new vector systems and delivery methods to overcome these issues, and are working on the development of targeted vectors that have the ability to Œhomeš to specific cardiovascular tissues.


Hartong R, Villareal F, Giordano FJ, Kim N, Brinker M, and Dillmann W: Phorbol Myristate Acetate Induced Hypertrophy of Neonatal Rat Cardiac Myocytes Is Associated With Decreased Sarcoplasmic Reticulum Calcium ATPase (SERCA2) Gene Transcription. JMCC 28:2467-2477, 1996.

Mestril R, Giordano FJ, Conde AG, Dillmann WH: Adenovirus Mediated Gene Transfer of Heat Shock Protein 70 (HSP70i) Protects Against Simulated Ischemia; JMCC 28:2351-2358, 1996.

Villareal F, Lee A, Dillmann WH and Giordano FJ: Adenovirus Mediated Overexpression of Human Transforming Growth Factor-b1 in Rat Cardiac Fibroblasts, Myocytes and Smooth Muscle Cells; JMCC 28 :735-742, 1996.

Giordano FJ, Ping P, McKirnan MD, Nozaki S, DeMaria AN, Dillmann WH, Mathieu-Costello O, and Hammond HK: Intracoronary Gene Transfer of Fibroblast Growth Factor-5 Increases Blood Flow and Contractile Function In An Ischemic Region of the Heart; Nature Medicine,: 2 :534-539, 1996.

Lu C-Y, Giordano FJ, Rogers K and Rothman A: Adenovirus Mediated Increase of Exogenous and Inhibition of Endogenous Fos-B Gene Expression in Cultured Pulmonary Artery Smooth Muscle Cells; JMCC. 28:1703-1713, 1996.

He H, Giordano FJ, Sayen MR, McDonnough PM, Rockman H, Hilal-Dandan R, Dillmann WH: Overexpression of Sarcoplasmic Reticulum Calcium ATPase in Transgenic Mice Accelerates Calcium Uptake by SR and Cardiac Relaxation; JCI, 100:380-389, 1997.

Giordano FJ, He H, McDonnough PM, Hilal-Dandan R, Meyer M, Sayen MR and Dillmann WH: Adenovirus Mediated Reconstitution and Overexpression of Sarcoplasmic Reticulum Calcium ATPase in Rat Cardiomyocytes; Circulation, 96:400-403, 1997.

Lu C-Y, Giordano FJ, Rogers K and Rothman A: Antisense fosB RNA inhibits thrombin-induced hypertrophy in cultured pulmonary arterial smooth muscle cells; . Circulation, 98:596-603, 1998.

Meyer M, Bluhm WF, He H, Post S, Giordano FJ, Lew W, Kranius EG, Dillmann WH. Phospholamban-to-SERCA2 ratio controls the force-frequency relationship. AJP;Heart; 276:H779-H785, 1999.

Hellerbrand C, Stefanovic B, Giordano F, Brenner DA. The role of TGFb1 in initiating hepatic stellate cell activation in vivo. Journal of Hepatology; 30:77-87, 1999.

Dunn KC, Marmorstein AD, Bonilha VL, Rodriguez-Boulan E, Giordano FJ, Hjelmeland LM. Use of the ARPE-19 Cell Line as a Model Of RPE Polarity: Basolateral Secretion of FGF5. IVOS; 39:2744-2749, 1998.

Henry TD, Rocha-Singh K, Isner JM, Kereiakes DJ, Giordano FJ, Simons M, Losordo DW, Hendel RC, Bonow RO, McCluskey ER. Initial Results of Intracoronary Administration of Recombinant Human Vascular Endothelial Growth Factor (rhVEGF); (submitted).

Eppler SM, McCluskey ER, Bloedow DC, Henry TD, Simons M, Giordano FJ, Zioncheck TF. Blood pressure changes and pharmacokinetics following vascular endothelial growth factor (rhVEGF) infusion in humans; (In preparation).

Giordano FJ, Katragadda R, Rothman A, Lu C-Y: INK4B gene expression induces apoptosis in vascular smooth muscle cells and morphometric changes in cardiac myocytes and skeletal myoblasts; (In preparation).

Giordano FJ, Ross Jr J, Peterson KL, Dalton N, McCluskey T, Zionchek T, McKirnan MD: Infusion of VEGF by Intracoronary or Intravenous Route Ameliorates Ischemia Induced Contractile Abnormalities in the Pig; (In preparation).

Simons M, Giordano FJ, Henry TD, Powell JS, Azrin MA, Kereiakes DJ, Annex B, Miller JM, Gibson CM, Lewin HC, Berman DS, McCluskey ER: Intravenous administration of recombinant human vascular endothelial growth factor (rhVEGF) in patients with ischemic heart disease; (In preparation).

Copyright © 2000, Yale University, New Haven, Connecticut, USA.
All rights reserved. Comments or suggestions to site editor.
Certifying authority:

Last modified: Friday, 12-Dec-2003 08:57:28 EST (PL).