PMID- 22134887
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20141120
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 4
DP  - 2012 Apr
TI  - Chemical reduction of carboxyl groups in heparin abolishes its vasodilatory 
      activity.
PG  - 1359-67
LID - 10.1002/jcb.24008 [doi]
AB  - Previous studies have shown that heparin induces vascular relaxation via 
      integrin-dependent nitric oxide (NO)-mediated activation of the muscarinic 
      receptor. The aim of this study was to identify the structural features of 
      heparin that are necessary for the induction of vasodilatation. To address this 
      issue, we tested heparin from various sources for their vasodilatation activities 
      in the rat aorta ring. Structural and chemical characteristics of heparin, such 
      as its molecular weight and substitution pattern, did not show a direct 
      correlation with the vasodilation activity. Principal component analysis (PCA) of 
      circular dichroism (CD), (1)H-nuclear magnetic resonance (NMR) and vasodilation 
      activity measurements confirmed that there is no direct relationship between the 
      physico-chemical nature and vasodilation activity of the tested heparin samples. 
      To further understand these observations, unfractionated heparin (UFH) from 
      bovine intestinal mucosa, which showed the highest relaxation effect, was 
      chemically modified. Interestingly, non-specific O- and N-desulfation of heparin 
      reduced its anticoagulant, antithrombotic, and antihemostatic activities, but had 
      no effect on its ability to induce vasodilation. On the other hand, chemical 
      reduction of the carboxyl groups abolished heparin-induced vasodilation and 
      reduced the affinity of heparin toward the extracellular matrix (ECM). In 
      addition, dextran and dextran sulfate (linear non-sulfated and highly sulfated 
      polysaccharides, respectively) did not induce significant relaxation, showing 
      that the vasodilation activity of polysaccharides is neither charge-dependent nor 
      backbone unspecific. Our results suggest that desulfated heparin molecules may be 
      used as vasoactive agents due to their low side effects.
CI  - (c) 2011 Wiley Periodicals, Inc.
FAU - Paredes-Gamero, Edgar J
AU  - Paredes-Gamero EJ
AD  - Departamento de Bioquimica, Universidade Federal de Sao Paulo, Rua Tres de Maio 
      100, 04044-020, Sao Paulo, SP, Brazil. edgar.gamero@unifesp.br
FAU - Medeiros, Valquiria P
AU  - Medeiros VP
FAU - Lima, Marcelo A
AU  - Lima MA
FAU - Accardo, Camila M
AU  - Accardo CM
FAU - Farias, Eduardo H C
AU  - Farias EH
FAU - Sassaki, Guilherme I
AU  - Sassaki GI
FAU - Campana, Patricia T
AU  - Campana PT
FAU - Miranda, Antonio
AU  - Miranda A
FAU - Ferreira, Alice T
AU  - Ferreira AT
FAU - Tersariol, Ivarne L S
AU  - Tersariol IL
FAU - Nader, Helena B
AU  - Nader HB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Vasodilator Agents)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/physiology
MH  - Cattle
MH  - Circular Dichroism
MH  - Heparin/*chemistry/pharmacology
MH  - In Vitro Techniques
MH  - Intestinal Mucosa/chemistry
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Molecular Weight
MH  - Multivariate Analysis
MH  - Principal Component Analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Spectrophotometry, Ultraviolet
MH  - Vasodilator Agents/*chemistry/pharmacology
EDAT- 2011/12/03 06:00
MHDA- 2012/10/12 06:00
CRDT- 2011/12/03 06:00
PHST- 2011/12/03 06:00 [entrez]
PHST- 2011/12/03 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
AID - 10.1002/jcb.24008 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Apr;113(4):1359-67. doi: 10.1002/jcb.24008.