scholarly journals Effects of remote ischemic preconditioning (RIPC) and chronic remote ischemic preconditioning (cRIPC) on levels of plasma cytokines, cell surface characteristics of monocytes and in-vitro angiogenesis: a pilot study

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Lars Hummitzsch ◽  
Karina Zitta ◽  
Lena Fritze ◽  
Jonas Monnens ◽  
Patrick Vollertsen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Surface ◽  
Ischemic Preconditioning ◽  
Surface Characteristics ◽  
Tube Formation ◽  
Remote Ischemic Preconditioning ◽  
Humoral Factors ◽  
Cardiovascular Protection ◽  
In Vitro Angiogenesis

AbstractRemote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm. Plasma and peripheral blood monocytes were isolated before RIPC (Control), after 1 × RIPC (RIPC) and at the end of 1 week of daily RIPC (cRIPC) treatment. Plasma concentrations of potentially pro-angiogenic humoral factors (CXCL5, Growth hormone, IGFBP3, IL-1α, IL-6, Angiopoietin 2, VEGF, PECAM-1, sTie-2, IL-8, MCSF) were measured using custom made multiplex ELISA systems. Tube formation assays for evaluation of in-vitro angiogenesis were performed with donor plasma, monocyte conditioned culture media as well as IL-1α, CXCL5 and Growth hormone. The presence of CD14, CD16, Tie-2 and CCR2 was analyzed on monocytes by flow cytometry. Employing in-vitro tube formation assays, several parameters of angiogenesis were significantly increased by cRIPC plasma (number of nodes, P < 0.05; number of master junctions, P < 0.05; number of segments, P < 0.05) but were not influenced by culture medium from RIPC/cRIPC treated monocytes. While RIPC/cRIPC treatment did not lead to significant changes of the median plasma concentrations of any of the selected potentially pro-angiogenic humoral factors, in-depth analysis of the individual subjects revealed differences in plasma levels of IL-1α, CXCL5 and Growth hormone after RIPC/cRIPC treatment in some of the volunteers. Nevertheless, the positive effects of RIPC/cRIPC plasma on in-vitro angiogenesis could not be mimicked by the addition of the respective humoral factors alone or in combination. While monocyte conditioned culture media did not affect in-vitro tube formation, flow cytometry analyses of circulating monocytes revealed a significant increase in the number of Tie-2 positive and a decrease of CCR2 positive monocytes after RIPC/cRIPC (Tie-2: cRIPC, P < 0.05; CCR2: RIPC P < 0.01). Cardiovascular protection may be mediated by RIPC and cRIPC via a regulation of plasma cytokines as well as changes in cell surface characteristics of monocytes (e.g. Tie-2). Our results suggest that a combination of humoral and cellular factors could be responsible for the RIPC/cRIPC mediated effects and that interindividual variations seem to play a considerable part in the RIPC/cRIPC associated mechanisms.

scholarly journals Influence of Hyperglycemia and Diabetes on Cardioprotection by Humoral Factors Released after Remote Ischemic Preconditioning (RIPC)

2021 ◽  
Vol 22 (16) ◽  
pp. 8880
Author(s):  
Carolin Torregroza ◽  
Lara Gnaegy ◽  
Annika Raupach ◽  
Martin Stroethoff ◽  
Katharina Feige ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Limb Ischemia ◽  
Remote Ischemic Preconditioning ◽  
Humoral Factors

Remote ischemic preconditioning (RIPC) protects hearts from ischemia–reperfusion (I/R) injury in experimental studies; however, clinical RIPC trials were unsatisfactory. This discrepancy could be caused by a loss of cardioprotection due to comorbidities in patients, including diabetes mellitus (DM) and hyperglycemia (HG). RIPC is discussed to confer protective properties by release of different humoral factors activating cardioprotective signaling cascades. Therefore, we investigated whether DM type 1 and/or HG (1) inhibit the release of humoral factors after RIPC and/or (2) block the cardioprotective effect directly at the myocardium. Experiments were performed on male Wistar rats. Animals in part 1 of the study were either healthy normoglycemic (NG), type 1 diabetic (DM1), or hyperglycemic (HG). RIPC was implemented by four cycles of 5 min bilateral hind-limb ischemia/reperfusion. Control (Con) animals were not treated. Blood plasma taken in vivo was further investigated in isolated rat hearts in vitro. Plasma from diseased animals (DM1 or HG) was administered onto healthy (NG) hearts for 10 min before 33 min of global ischemia and 60 min of reperfusion. Part 2 of the study was performed vice versa—plasma taken in vivo, with or without RIPC, from healthy rats was transferred to DM1 and HG hearts in vitro. Infarct size was determined by TTC staining. Part 1: RIPC plasma from NG (NG Con: 49 ± 8% vs. NG RIPC 29 ± 6%; p < 0.05) and DM1 animals (DM1 Con: 47 ± 7% vs. DM1 RIPC: 38 ± 7%; p < 0.05) reduced infarct size. Interestingly, transfer of HG plasma showed comparable infarct sizes independent of prior treatment (HG Con: 34 ± 9% vs. HG RIPC 35 ± 9%; ns). Part 2: No infarct size reduction was detectable when transferring RIPC plasma from healthy rats to DM1 (DM1 Con: 54 ± 13% vs. DM1 RIPC 53 ± 10%; ns) or HG hearts (HG Con: 60 ± 16% vs. HG RIPC 53 ± 14%; ns). These results suggest that: (1) RIPC under NG and DM1 induces the release of humoral factors with cardioprotective impact, (2) HG plasma might own cardioprotective properties, and (3) RIPC does not confer cardioprotection in DM1 and HG myocardium.

scholarly journals The release of cardioprotective humoral factors after remote ischemic preconditioning in humans is age- and sex-dependent

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
André Heinen ◽  
Friederike Behmenburg ◽  
Aykut Aytulun ◽  
Maximilian Dierkes ◽  
Lea Zerbin ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Remote Ischemic Preconditioning ◽  
Humoral Factors ◽  
Age And Sex

scholarly journals Cardiomyocyte mitochondria as targets of humoral factors released by remote ischemic preconditioning

2017 ◽  
Vol 2 ◽  
pp. 448-458 ◽  
Author(s):  
Nilguen Gedik ◽  
Leonardo Maciel ◽  
Christiane Schulte ◽  
Andreas Skyschally ◽  
Gerd Heusch ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Remote Ischemic Preconditioning ◽  
Humoral Factors

scholarly journals JunB is required for endothelial cell morphogenesis by regulating core-binding factor β

2006 ◽  
Vol 175 (6) ◽  
pp. 981-991 ◽  
Author(s):  
Alexander H. Licht ◽  
Oliver T. Pein ◽  
Lore Florin ◽  
Bettina Hartenstein ◽  
Hendrik Reuter ◽  
...  
Keyword(s):  
Target Gene ◽  
Tube Formation ◽  
Cell Morphogenesis ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Endothelial Functions ◽  
Runx Proteins ◽  
In Vitro Angiogenesis

The molecular mechanism triggering the organization of endothelial cells (ECs) in multicellular tubules is mechanistically still poorly understood. We demonstrate that cell-autonomous endothelial functions of the AP-1 subunit JunB are required for proper endothelial morphogenesis both in vivo in mouse embryos with endothelial-specific ablation of JunB and in in vitro angiogenesis models. By cDNA microarray analysis, we identified core-binding factor β (CBFβ), which together with the Runx proteins forms the heterodimeric core-binding transcription complex CBF, as a novel JunB target gene. In line with our findings, expression of the CBF target MMP-13 was impaired in JunB-deficient ECs. Reintroduction of CBFβ into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFβ in EC morphogenesis.

scholarly journals Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway

2020 ◽  
Vol 21 (5) ◽  
pp. 1692 ◽  
Author(s):  
Muntasir Billah ◽  
Anisyah Ridiandries ◽  
Usaid K Allahwala ◽  
Harshini Mudaliar ◽  
Anthony Dona ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Mammalian Cells ◽  
Glycogen Synthase ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Janus Kinase ◽  
Remote Ischemic Preconditioning ◽  
Dependent Manner ◽  
Stat Pathway

Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3β) pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.

Anti-angiogenesis mediated by angiostatin K1–3, K1–4 and K1–4.5

2006 ◽  
Vol 95 (04) ◽  
pp. 668-677 ◽  
Author(s):  
Ya-Huey Chen ◽  
Hua-Lin Wu ◽  
Ching Li ◽  
Yi-Hsien Huang ◽  
Chi-Wu Chiang ◽  
...  
Keyword(s):  
P53 Protein ◽  
Expression System ◽  
Mrna Level ◽  
Integrin Αvβ3 ◽  
Tube Formation ◽  
Multiple Forms ◽  
Human Endothelial Cells ◽  
Downstream Effectors ◽  
In Vitro Angiogenesis

SummaryThe molecular mechanism mediated by multiple forms of angiostatin via acting on proliferating vascular endothelium remains elusive. To address whether three forms of angiostatin, K1-3, K1-4 or K1-4.5, utilized similar or distinct pathways to mediate anti-angiogenesis, we adopted an adenoviral expression system to express secretable angiostatin molecules for CM collection. The anti-angiogenic activity of K1-3, K1-4 or K1-4.5 was confirmed by using proliferation, migration, tube formation and apoptotic assays of human endothelial cells. These angiostatin molecules at comparable expression level inhibited various in vitro angiogenesis assays with some variations. Furthermore, K1-3, K1-4 or K1-4.5 increased the expression of p53 protein and its downstream effectors, enhanced FasL-mediated signaling pathways, and decreased activation of AKT. At least three different receptors, Fas, integrin αvβ3 and ATP synthase, were involved in the anti-angiogenic action of angiostatin molecules. Besides, the expression of 189 genes at mRNA level was significantly altered by K1-3, K1-4 or K1-4.5. More than 70% of these genes participate in growth, inflammation, apoptosis, migration and extracellular matrix. Taken together, K1-3, K1-4 and K1-4.5, regardless of the number of kringles in the angiostatin molecules, mediated anti-angiogenesis via mostly similar pathways. We are the first to demonstrate the involvement of DAPK1 in the mediation of anti-angiogenesis by angiostatin.

scholarly journals Autocrine Role for Interleukin-8 in Bartonella henselae-Induced Angiogenesis

2006 ◽  
Vol 74 (9) ◽  
pp. 5185-5190 ◽  
Author(s):  
Amy M. McCord ◽  
Sandra I. Resto-Ruiz ◽  
Burt E. Anderson
Keyword(s):  
Endothelial Cells ◽  
Capillary Tube ◽  
Bartonella Henselae ◽  
Tube Formation ◽  
Interleukin 8 ◽  
Endothelial Cell Proliferation ◽  
Chemokine Receptor Cxcr2 ◽  
In Vitro Angiogenesis

ABSTRACT The gram-negative bacterium Bartonella henselae is capable of causing angiogenic lesions as a result of infection. Previously, it has been shown that B. henselae infection can result in production of the chemokine interleukin-8 (IL-8). In this study, we demonstrated that monocytes, endothelial cells, and hepatocytes produce IL-8 in response to B. henselae infection. We also investigated the role of IL-8 in B. henselae-induced endothelial cell proliferation and capillary tube formation. Both in vitro angiogenesis assays were IL-8 dependent. B. henselae-mediated inhibition of apoptosis, as indicated by gene expression of Bax and Bcl-2, was also shown to be IL-8 dependent in endothelial cells. Furthermore, infection of endothelial cells with B. henselae stimulated upregulation of the IL-8 chemokine receptor CXCR2. Infection of human endothelial cells by B. henselae resulting in IL-8 production likely plays a central role in the ability of this organism to cause angiogenesis during infection.

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