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About Sickkids
About SickKids

Aleksander Hinek, MD, PhD, DSc

Research Institute
Senior Scientist
Translational Medicine

University of Toronto
Professor
Department of Laboratory Medicine & Pathobiology

Professor
Institute of Medical Science


Phone: 416-813-6725
Fax: 416-813-7480
Email: alek.hinek@sickkids.ca

Research Interests

  • Elastin and other components of extracellular matrix
  • Atherosclerosis/vascular Injury
  • Inherited cardiovascular diseases
  • Tissue regeneration
  • Bioengineering

Research Activities

My previous research interests were scattered through a broad spectrum of subjects, centred around structure and function of connective tissue cells and the extracellular matrix, in the development of disease. I studied problems arising with cartilage and bone transplantation and bioengineering of cartilage from human cells. I have addressed pathomorphology of vascular diseases including atherosclerosis and diabetic arteriopathies, protection of cardiac muscle against cytotoxicity induced by anticancer drugs, and role of proteinases in cancer spreading and metastasis. Many of my studies were aimed at ultrastructure of elastic fibers, and role of impaired elastogenesis in pathological processes ranging from cancer spreading and wound healing to atherosclerosis. They lead to the discovery of the 67-kD elastin binding protein (EBP), which is the alternatively spliced variant of beta-galactosidase (S-GAL) and serves as a major subunit of the cell surface "elastin receptor" propagating multiple intracellular signals. EBP also serves as a recyclable intracellular chaperone facilitating secretion of tropoelastin and assembly of elastic fibers.

My research team and I found that primary or secondary deficiencies in the EBP can be linked to impaired elastin deposition that directly contributes to the development of cardiovascular defects, supravalvular aortic stenosis, occlusions of coronaries, and skeletal deformities in children with such inherited conditions as GM1-gangliosidosis, Morquio B disease, Costello syndrome, Hurler disease, and Williams-Beuren syndrome. Another set of recent results indicates that the second components subunit of the elastin receptor (Neuraminidase-1) also facilitates elastic fiber assembly and may modulate mitogenic response of arterial SMC to mitogenic growth factors IGF-II and PDGF.

We have also verified that a third component of cell surface elastin receptor, called Protective Protein, has deamidase activity that may inactivate a potent SMC mitogen and vasoconstrictor, Endothelin 1, thereby controling arterial blood pressure. Recently we have discovered that aldosterone also induces elastin production in cardiac fibroblasts through activation of IGF-1 receptor and explained why inhibition of mineralo-corticosteroid receptors triggers the beneficial remodeling of the injured heart.

Future Research Interests

Pursuing our discovery that subunits of elastin receptor modulate normal production of elastic fibers and control cellular proliferation, we will determine whether overexpression of the EBP and activation of other sub-units of elastin receptor could be used in future therapies of children with inherited elastinopathies, including Williams-Beuren disease and Costello Syndrome. We will also therapeutically apply results our recent research indicating that low concentration of iron is a prerequisite for the transcription of elastin gene and that polyphenols, ellagic and tannic acids protect elastic fibers present in skin, lungs and arteries from enzymatic degradation.

We have also started new research aimed at pharmacological treatments of children with Marfan disease and Loyes-Dietz syndrome that are characterized with development or aortic aneurysms.

External Funding

  • Canadian Institutes for Health Research (CIHR)
  • Heart and Stroke Foundation of Ontario

Achievements

Career Investigator Award, Canadian Heart and Stroke Foundation, since 1993.

Publications

Mao S, Li W, Qa'aty N, Vincent M, Zhang M, Hinek A. Tanshinone IIA inhibits angiotensin II induced extracellular matrix remodeling in human cardiac fibroblasts--Implications for treatment of pathologic cardiac remodeling.  Int J Cardiol. 2016 Jan 1;202:110-7.

Qa'aty N, Vincent M, Wang Y, Wang A, Mitts TF, Hinek A. Synthetic ligands of the elastin receptor induce elastogenesis in human dermal fibroblasts via activation of their IGF-1 receptors.
J Dermatol Sci. 2015 Dec;80(3):175-85.  

Qa'aty N, Wang Y, Wang A, Mao S, Vincent M, Husain M, Hinek A. The anti-diabetic hormone glucagon-like peptide-1 induces formation of new elastic fibers in human cardiac fibroblasts after cross-activation of IGF-1R. Endocrinology. 2015 Jan;1(1):90-102. .

Mao S, Wang L, Zhao X, Shang H, Zhang M, Hinek A. Sodium tanshinone IIA sulfonate for reduction of periprocedural myocardial injury during percutaneous coronary intervention (STAMP trial): rationale and design . Int J Cardiol. 2015 Jan 3;182C: 329-333.

Hinek A, Kim HJ, Wang Y, Wang A, Mitts TF. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. J Dermatol Sci. 2014 Sep;75(3):173-82.

Mao,S., Wang,Y., Zhang,M., and Hinek,A. Phytoestrogen, tanshinone IIA  diminishes collagen deposition and stimulates new elastogenesis in cultures of human cardiac fibroblasts. Exp.Cell Res. 2014, 15 April; 323, (1),189–197

Lehman A, Mattman A, Sin D, Pare P, Zong Z, d’Azzo A, Campos Y, Sirrs S, and  Hinek A. Emphysema in an adult with galactosialidosis linked to a defect in primary elastic fiber assembly. Mol Genet Metab. 2012 May;106(1):99-103.

Shi J, Wang A, Sen S, Wang Y, Kim HJ, Mitts TF and Hinek A. Insulin Induces Production of New Elastin in Cultures of Human Aortic Smooth Muscle Cells. Am. J. Pathol. 180 (2):715-726, 2012.
Kluppel M, Samavarchi-Tehrani P, Liu K, Wrana JL and Hinek A. C4ST-1 / CHST11-controlled chondroitin sulfation mediates oncogenic HRAS signaling in Costello syndrome. Eur.J. Hum.Gen. 20: 870-877, 2012.

Lehman A, Mattman A, Sin D, Pare P, Zong Z, d’Azzo A, Campos Y, Sirrs S, Hinek A.  Emphysema in an adult with galactosialidosis is mechanistically linked to a defect in primary elastic fiber assembly. Molecular Genetics & Metabolism. 106(1), 99–103,2012.
BarnettCP, ChitayatD, BradleyTJ,Wang Y, and Hinek A. Dexamethasone normalizes aberrant elastic fibers production and collagen Isecretion by Loeys-Dietz syndrome fibroblasts –a possible treatment? Eur.J.Hum.Gen. 19:624-633, 2011.

Merrilees MJ,Beaumont BW, Braun KR, Thomas AC, Kang I, Hinek A, Passi A, Wight,TN.  Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage ccumulation. Atherosc. Thromb.Vasc.Biol. 31:1309-1316, 2011.

Sen S, Bunda S, Shi J, Wang A, Mitts TF, Hinek A. Retinoblastoma Protein Modulates the Inverse Relationship Between Cellular Proliferation and Elastogenesis. J. Biol. Chem. 286:36580-36591, 2011.

Pshezhetsky AV and Hinek A. Where Catabolism Meets Signalling: Neuraminidase 1 as a Modulator of Cell Receptors. Glycoconjugate J. 28(7):441-452,2011.

Arribas, SM, Hermida, C, Gonzalez, CM, Moreno, S, Briones, Wang, Y, Hinek, A. Enhanced Survival of Vascular Smooth Muscle Cells Accounts for Heightened Elastin Deposition in Arteries of Neonatal SHR. Experimental Physiology. 95 (4):550-560, 2010.

Arabkhari, M, Bunda, S, Wang, Y, Wang, A Pshezhetsky, AV, Hinek, A. Desialylation of Insulin Receptors and IGF-1 Receptors by Neuraminidase 1 controls the net proliferative response ofL6 myoblasts to insulin. Glycobiology. 20: 603-616,2010.

Mitts T, Bunda S, Wang Y, Hinek A. Aldosterone and Mineralocorticoid Receptor Antagonists Modulate Elastin and Collagen Deposition in Normal and Pathological Human Skin.  J. Investig. Dermatol. 130: 2396-2406, 2010.

Szauter K M,Ordas A,Laxer R M, Pope E, Wherrett D, Alman B, Mink M, Boyd C D, Csiszar K, Hinek A. A novel fibrotic disorder associated with increased dermal fibroblast proliferation and down regulation of genes of the microfibrillar network. Br. J. Dermatol. 63(5):1102-15, 2010.

Murphy BA, Bunda S, Mitts TF, and Hinek A. The Hyperthermia-Enhanced Association Between Tropoelastin And Its 67 Kda Chaperone Results In Better Deposition Of Elastic Fibers. J. Biol. Chem. 285:40282-40293, 2010