Perlecan on Vascular Smooth Muscle Cell Response to Arterial Injury

نویسندگان

  • Sang Yup Lim
  • Azriel B. Osherov
  • Rafael Wolff
  • Beiping Qiang
  • Ilana Erlich
  • Nafiseh Nili
  • Ya-Ting Chang
  • Karl Tryggvason
  • Suzanne L. Advani
  • Richard E. Gilbert
  • Bradley H. Strauss
چکیده

Heparan Sulfate Side Chains have a Critical Role in the Inhibitory Effects of 1 Perlecan on Vascular Smooth Muscle Cell Response to Arterial Injury 2 *Lara Gotha MSc, *Sang Yup Lim MD, PhD Azriel B. Osherov MD, Rafael Wolff 3 MD, Beiping Qiang MD, PhD, Ilana Erlich MD, Nafiseh Nili PhD, Sivaram 4 Pillarisetti PhD, Ya-Ting Chang MD, Phan-Kiet Tran MD, PhD, Karl Tryggvason 5 PhD, Ulf Hedin MD, PhD, Karin Tran-Lundmark MD, PhD, Suzanne L. Advani BSc, 6 Richard E. Gilbert MD, PhD, and Bradley H. Strauss MD, PhD 7 8 Schulich Heart Program, Sunnybrook Health Sciences Centre, Keenan Research Centre 9 in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, 10 Toronto, Ontario, Canada. Reddy US Therapeutics, Norcross, Georgia, USA. 4 Dept of 11 Pediatric Cardiac Surgery, Skane University Hospital, Lund, Sweden, Dept of Molecular 12 Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, Korea University 13 Ansan Hospital, Ansan, Korea; Current Address: Department of Cardiology, Barzilai 14 Medical Center, Ashkelon, Ben-Gurion University, Israel. 15 • co-primary authors 16 The study was funded by the Canadian Institute of Health Research and the Canada 17 Research Chair Program. Dr. Richard Gilbert is the Canada Research Chair in Diabetes 18 Complications. Drs Tran, Tran-Lundmark and Hedin were funded by Princess Lovisas’ 19 Research Foundation, Swedish Heart-Lung Foundation and Swedish Research Council. 20 Address for correspondence: Dr. Bradley H. Strauss, Reichmann Chair in Cardiovascular 21 Research, Schulich Heart Center, Sunnybrook Health Sciences Centre, D-406, 2075 22 Bayview Avenue, Toronto, Ontario, Canada, M4N 3M5 Telephone: (416) 480-6066, Fax: 23 (416) 480-6174, email:[email protected] 24 Words: 5737 25 Articles in PresS. Am J Physiol Heart Circ Physiol (May 23, 2014). doi:10.1152/ajpheart.00654.2013

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury.

Perlecan is a proteoglycan composed of a 470-kDa core protein linked to three heparan sulfate (HS) glycosaminoglycan chains. The intact proteoglycan inhibits the smooth muscle cell (SMC) response to vascular injury. Hspg2(Δ3/Δ3) (MΔ3/Δ3) mice produce a mutant perlecan lacking the HS side chains. The objective of this study was to determine differences between these two types of perlecan in modi...

متن کامل

Changes in perlecan expression during vascular injury: role in the inhibition of smooth muscle cell proliferation in the late lesion.

OBJECTIVE Vascular smooth muscle cells (SMCs), activated by growth factors after arterial injury, migrate and proliferate to expand the intima of the blood vessel. During intimal expansion, proliferation is suppressed and an increasingly large proportion of the neointimal mass is composed of newly synthesized extracellular matrix (ECM). We sough to determine whether the ECM heparan sulfate prot...

متن کامل

The role of perlecan in arterial injury and angiogenesis.

Perlecan is a large heparan sulfate proteoglycan (HSPG), which is a major component of the vessel wall. In relation to vascular biology, perlecan has been shown to be a potent inhibitor of smooth muscle cell (SMC) activity. In vivo experiments in animal models of arterial injury have shown that perlecan may inhibit thrombosis and intimal hyperplasia. On the other hand, perlecan has been shown t...

متن کامل

Endothelial Cells Provide Feedback Control for Vascular Remodeling Through a Mechanosensitive Autocrine TGF- Signaling Pathway

Mechanical forces are potent modulators of the growth and hypertrophy of vascular cells. We examined the molecular mechanisms through which mechanical force and hypertension modulate endothelial cell regulation of vascular homeostasis. Exposure to mechanical strain increased the paracrine inhibition of vascular smooth muscle cells (VSMCs) by endothelial cells. Mechanical strain stimulated the p...

متن کامل

Endothelial cells provide feedback control for vascular remodeling through a mechanosensitive autocrine TGF-beta signaling pathway.

Mechanical forces are potent modulators of the growth and hypertrophy of vascular cells. We examined the molecular mechanisms through which mechanical force and hypertension modulate endothelial cell regulation of vascular homeostasis. Exposure to mechanical strain increased the paracrine inhibition of vascular smooth muscle cells (VSMCs) by endothelial cells. Mechanical strain stimulated the p...

متن کامل

Mice deficient in tissue factor demonstrate attenuated intimal hyperplasia in response to vascular injury and decreased smooth muscle cell migration.

Tissue factor (TF) is the primary initiator of the coagulation cascade and is thought to play a key role in the generation of arterial thrombosis. Recent studies have suggested that TF mediates inflammatory processes in the arterial wall and may be an important regulator of intimal hyperplasia. We have employed genetically engineered mice (mTF(-/-) /hTF(+)) with markedly diminished TF activity ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2014