Modulation of peripheral inflammation by locally administered hemorphin-7

Sanderson, Katarina; Nyberg, Fred; Khalil, Zeinab

doi:10.1007/s000110050266

Cited by 48 publications

(18 citation statements)

References 50 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This protection was mediated by peripheral opioid receptors. 15,16 On the other hand, opioids may decrease infl ammation, 17,18 which is associated with atherogenesis and plaque disruption. [19][20][21][22] Thus, long-term opium exposure may decrease atherosclerosis directly and may protect against injury from ischemia and reperfusion, thereby mitigating damage from an infarct.…”

Section: Discussionmentioning

confidence: 98%

Effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery

Safaii

Kazemi

2010

Gen Thorac Cardiovasc Surg

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery

Safaii

Kazemi

2010

Gen Thorac Cardiovasc Surg

View full text Add to dashboard Cite

show abstract

“…14 These peptides are reported to be mainly generated by digestion of the hemoglobin ␤-chain by cathepsin D. 9 They were isolated from brain, 17 lung, 18 and biological fluids, 13 and they display various biological activities such as angiotensin-converting enzyme inhibition, 19 opioid-like functions, 20 and modulation of inflammation. 12 They also possess analgesic properties. 13 Serum H7 peptides have been already assayed and found to be decreased in patients with breast cancer 21 and in patients with diabetes.…”

Section: Discussionmentioning

confidence: 99%

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Dejouvencel

Feron

Rossignol

et al. 2010

ATVB

View full text Add to dashboard Cite

Objective-In human abdominal aortic aneurysm, the accumulation of blood-derived cells and proteases within the mural thrombus plays a pivotal role in the evolution toward vessel wall rupture. We sought to identify peptides released from abdominal aortic aneurysm specimens, characterized by an intraluminal thrombus. Methods and Results-Intraluminal thrombus samples were analyzed by differential proteomics, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A 1309-Da peptide was detected in larger amounts in the newly formed luminal thrombus layer relative to older layers. It was identified as being LVVYPWTQRF (known as LVV-Hemorphin 7), a peptide generated from hemoglobin by cathepsin D. By immunohistochemical analysis, we showed that Hemorphin 7 (H7) colocalizes with cathepsin D and cathepsin G in the luminal layer of the intraluminal thrombus. In vitro, cathepsin G was able to generate H7 peptides at pH 7.4, whereas cathepsin D was only active in acidic conditions. Finally, H7 peptides were shown to be increased 3-to 4-fold in sera of abdominal aortic aneurysm patients relative to controls, and their levels were positively correlated with the volume of the thrombus. Key Words: Human atherothrombosis Ⅲ cathepsin G Ⅲ cathepsin D Ⅲ circulating biomarker Ⅲ thrombus I n human atherothrombosis, the accumulation of bloodderived cells and zymogens contributes to oxidation and proteolysis, together leading to arterial wall destabilization. 1 Depending on the arterial territory, complications associated with atherosclerosis may evolve toward stenosis, frequent in carotid, coronary, and femoral arteries, or outward remodeling, mainly in the aorta. In abdominal aorta, where atherothrombosis frequently develops, evolution toward aneurysm is characterized by the presence of a dynamic intraluminal mural thrombus (ILT), which represents a source of blood-borne proteases participating in extracellular matrix degradation and smooth muscle cell apoptosis, preventing thrombus colonization and cicatrization. 2,3 In the present study, we aimed to look for biomarkers reflecting the pathological remodeling of aortic atherothrombosis associated with the thrombus in abdominal aortic aneurysm (AAA). For this purpose, we used a differential proteomics approach comparing the different layers of human AAA samples, including the thrombus, and the remaining media. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), a particularly well-suited technology for detection of peptides and small proteins, including proteolytic fragments. Our hypothesis is that the proteases conveyed by leukocytes (matrix metalloproteases, elastase, cathepsins, etc) or those generated in situ (ie, plasmin, thrombin) may produce protein fragments reflecting the pathological vascular remodeling. 4 Our strategy was thus to compare the profiles of low-molecular-weight proteins and peptides released by AAA samples. Such peptides could be used as biomarkers of the thrombus activity and an...

show abstract

“…b-endorphin, as anti-inflammatory neuropeptides and MOR agonists, down regulates the inflammatory processes by shifting Th1/Th2 balance towards Th2 [51]. Importantly, hemorphin-7 was reported to inhibit the acute inflammatory response to SP by binding to MOR [18]. It should be underscore that SP is potent stimulator of pro-inflammatory cytokines (IL-1, IL-6 and TNFa) production [52].…”

Section: Discussionmentioning

confidence: 93%

“…Functional interactions have been described between hemorphins on the one hand and b-endorphin, growth hormone, prolactin [7], substance P (SP) [18], neuropeptide Y, Met-ENK-Arg-Phe [19] and CRF [17] on the other hand. It has been found out that central CRF and opioid pathways are involved in the interaction between LVVhemorphin-7 and brain serotonergic system [17].…”

Section: Introductionmentioning

confidence: 99%

Hemorphins Act as Homeostatic Agents in Response to Endotoxin-Induced Stress

et al. 2009

View full text Add to dashboard Cite

The effect of synthetic LVV-hemorphin-7 and hemorphin-7 on hypothalamo-pituitary-adrenocortical axis activity in response to endotoxin-induced stress was studied. The intraperitoneal (ip) endotoxin (lipopolysaccaride, LPS) (0.5 mg/kg) administration in combination with hemorphin (1 mg/kg) induce significant decrease in plasma corticosterone and modest decrease in plasma levels of tumor necrosis factor-alpha (TNFalpha) in compare with elevated levels of both corticosterone and TNFalpha in plasma of rats received LPS administration alone. Increased activity of calcineurin in both plasma and brain of rats received ip administration of LPS, was recovered under LPS + hemorphin treatment. In two independent proteome analysis, using 2-dimensional fluorescence difference gel electrophoresis and the isotope coded protein label technology, peptidyl-prolyl cis-trans-isomerase A (cyclophilin A) was identified as regulated by hemorphins protein in mouse brain. A therapeutic potential of hemorphins and mechanisms of their homeostatic action in response to endotoxin-induced stress are discussed.

show abstract

Modulation of peripheral inflammation by locally administered hemorphin-7

Cited by 48 publications

References 50 publications

Effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery

Effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Hemorphins Act as Homeostatic Agents in Response to Endotoxin-Induced Stress

Contact Info

Product

Resources

About