Endogenous heparin levels in the controlled asthmatic patient

Abstract

Levels of circulating endogenous heparin in patients with diseases associated with inflammatory processes, such as asthma, are still unknown. Since heparin displays antiinflammatory properties, it is expected that the inhibitory effects on inflammatory mediators are reduced at low levels of endogenous heparin. 1 We present evidence supporting the hypothesis that asthmatic patients have lower levels of circulating endogenous heparin than healthy individuals have.Since 1955, endogenous plasma heparin has been demonstrated to be a normal constituent of blood, with concentrations ranging from 153 to 177 mIU/ml, and its levels were found to be independent of gender or age.2 Discrepancies in the concentrations of endogenous heparin reported by various research groups are thought to result from the different quantitative methods or isolation procedures used.

Design of growth factor sequestering biomaterials

“…130 Additionally, the same substrates increased hMSC osteogenic differentiation in a BMP signaling-dependent fashion in serum-containing osteogenic induction medium, again without supplemented GFs. 130 These studies suggested that endogenous circulating heparin, previously identified as a component of human blood plasma, 153,154 harnessed at engineered 2D interfaces could enrich and enhance the activity of endogenous GFs while foregoing the need for exogenous supplemented GFs.…”

“…71 Further characterization will be required to determine whether GF sequestering with heparin-binding peptides (e.g. ATIII, PF4Zip, Hep-BP1-5, HEPpep) is a result of direct interactions with the GF or by indirect interactions with endogenous heparin or HS 153,154 in culture.…”

“…Further, VEGF and FGF-2 co-delivery with HBPA nanofibers significantly increased pancreatic endothelial cell sprouting relative to GFs alone 160 , suggesting that the heparin-binding nanofibers potentiated the effect of VEGF and FGF-2 by sequestering endogenous heparin or HS and supplemented GFs. Here, we refer to endogenous heparin or HS as a soluble glycosaminoglycan in blood plasma 153,154 , a component of the heparin proteoglycan serglycin secreted by mast cells during an inflammatory response 161 ( e.g. during wound healing), or a component of immobilized cell membrane heparan sulfate proteoglycans in the pericellular space 13,162 .…”

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: Insights into the physiological role of endogenous heparin

“…It is of interest therefore that patients with allergy, where there is regular mast cell degranulation in response to sensitising allergens, have been reported to have increased levels of "circulating heparin like material" (41) which may account for the observations that atopic patients can have a mild haemostatic defect (42), and even have evidence of less calcification of their arteries (43). However, more recent observations have suggested that there may a loss of heparin in the circulation of patients with asthma (44) and that some patients can have a hyper-coaguable state (45).…”

Pharmacology of Heparin and Related Drugs

“…This group (Brunnee et al 1997;Nogi et al 1999) suggested that in allergic reactions mast cellderived heparin can act as a suitable surface to promote this cascade and can contribute to the generation of kinins to participate in the allergic response. However, a small clinical study compared plasma levels of endogenous heparin-like material between a group of patients with controlled asthma and healthy controls and found these levels to be reduced in the patient group; the authors conclude that the lack of heparin-associated anti-inflammatory activity in these individuals may be a significant factor in the disease (Davids et al, 2010).…”