Development of new heparin-like compounds and other antithrombotic drugs and their interaction with vascular endothelial cells

Abstract

The anticlotting and antithrombotic activities of heparin, heparan sulfate, low molecular weight heparins, heparin and heparin-like compounds from various sources used in clinical practice or under development are briefly reviewed. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate from Artemia franciscana and a dermatan sulfate from tuna fish show a potent heparin cofactor II activity. A heparan sulfate derived from bovine pancreas has a potent antithrombotic activity in an arterial and venous thrombosis model with a negligible activity upon the serine proteases of the coagulation cascade. It is suggested that the antithrombotic activity of heparin and other antithrombotic agents is due at least in part to their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate.

Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo

“…However, only between 15 and 25% of the shorter fragments present in LMWH contain this sequence (Lindahl et al, 1979;Lane et al, 1984;Hirsh, 1998;Herault et al, 2002). The variation in the occurrence of the pentasaccharide between LMWHs results in differences in their ability to bind AT and therefore in inhibiting factor Xa (Nader et al, 2001). The cleavage of heparin required to produce oligosaccharides is likely to disrupt many of these sequence motifs, reducing the number available for AT binding within a given weight of the processed material.…”

<b>Extraction and structural properties of <i>Acanthophora muscoides </i>(Rhodophyceae) extracellular matrix sulfated polysaccharides and their effects on coagulation

“…Although crucial in clinical thrombotic events, unfractionated heparin (UHEP), a 1,4-linked linear glycosaminoglycan variously sulfated consisting of β-D-glucosamine (N-sulfated or acetylated) and uronic acid (β-D-glucuronic acid or α-L-iduronic acid) residues, and extracted from animal tissues, manifests extensive bleeding side effects (mainly hemorrhage) (Nader et al, 2001). Additionally, the alarming report of UHEP that has been contaminated with glycosaminoglycan oversulfated chondroitin sulfate (inducing hypotension) and some fatal events during the "UHEP crisis" (Pomin, 2012) have caused a pressing need to search novel specific glycans from renewable sources displaying analogies with UHEP (Leite et al, 1998;Athukorala, Jung, Vasanthan, & Jeon, 2006;Dantas-Santos et al, 2012;Pomin, 2012;Rodrigues et al, 2013;Mourão, 2015;Ustyuzhanina et al, 2016 The genus Acanthopohra J. V. F. Lamouroux (Rhodomelaceae, Ceramiales) of red algae shows a discontinuous pattern of global distribution.…”

Isolamento, fracionamento e atividade anticoagulante de iota-carragenanas da Solieria filiformis

“…Entretanto, a administração terapêutica continuada da HEP, na prevenção e tratamento de distúrbios tromboembólicos, é potencialmente acompanhada por vários fatores adversos, citando-se, por exemplo, a hemorragia, a trombocitopenia, a síndrome da trombocipotenia induzida por HEP com complicações trombóticas e o I Rede Nordeste de Biotecnologia, Fortaleza, Ceará, Brasil. risco de contaminação viral, já que é obtida de animais (NADER et al, 2001). Mais recentemente, MELO et al (2008) alertaram ainda para o fato da baixa qualidade de algumas preparações de HEPs usadas em cirurgias cardíacas com circulação extracorpórea no Brasil, podendo assim induzir hipotensão e aumento significativo dos efeitos colaterais da HEP nos pacientes.…”