Impairment of Endothelial Cell Function Induced by Hemoglobin A1c and the Potential Mechanisms

Bo, Jinshuang; Guan, Yanfei; Guo, Yan; Shen, Xie; Zhang, C.; Zhang, H.; Chen, Z.; Lü, Jianxin; Meng, Qing H.

doi:10.1055/s-0035-1554622

Cited by 4 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 24 h in culture, PHb did not influence the migratory capacity of C2C12 cells. Thus, we decided to prolong the assay for an additional 24 h. After 48 h, PHb slightly inhibited the migration of these cells, which is in accordance with a previous study that showed that HbA1c, glycated hemoglobin isolated from patients with type 2 diabetes, reduced the migration of HUVEC cells in a dose-and time-dependent manner [48]. Also, it was reported that two peptides derived from BHb blocked about 50% and 30% wound closure in a scratch assay of the MIAPaCa-2 cell line when compared to the control group after treating for 72 h [37].…”

Section: Discussionsupporting

confidence: 84%

Extracellular xenogeneic hemoglobin suppresses the capacity for C2C12 myoblast myogenic differentiation

Stančić

Drvenica

Bugarski

et al. 2020

ARCH BIOL SCI BELGRA

View full text Add to dashboard Cite

Functional characteristics of satellite cells (SCs) that act as myogenesis initiators and have emerged as a promising target for cell therapy, are dependent on their microenvironment. The aim of this study was to investigate the effect of cell-free hemoglobin, as a part of the microenvironment of SCs, on their functional characteristics. The C2C12 cell line served as the experimental model of the SC experimental model; hemoglobin isolated from porcine (PHb) and bovine (BHb) slaughterhouse blood served as the extracellular hemoglobin. The proliferation rate of C2C12 cells was assessed by the MTT test, migration capacity by the scratch assay, and myogenic differentiation capacity by histochemical staining and RT-PCR analysis of the expression of genes specific for myogenic lineage. The effect of hemoglobin on the proliferation and migration of C2C12 cells was dependent on its concentration and the animal species it was isolated from, but the effect of BHb was more prominent. Both PHb and BHb decreased the expression levels of myogenin and muscle specific creatine kinase at a 10 ?M concentration. While PHb had no effect on the morphometric parameters of C2C12 myotubes, BHb modified the area and length of C2C12 myotubes cultivated in DMEM/2% horse serum and DMEM/10% fetal calf serum. While PHb and BHb had no effect on heme oxygenase 1 (Hmox1) expression, they stimulated the expression of hypoxia-inducible factor 1-alpha (Hif1?) at a concentration of 10 ?M. The mainly inhibitory effect of cell-free hemoglobin on myogenic differentiation suggests that it could be a relevant factor in the outcome of cell therapy of muscle injury. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 451-03-68/2020-14/200015]

show abstract

Section: Discussionsupporting

confidence: 84%

Extracellular xenogeneic hemoglobin suppresses the capacity for C2C12 myoblast myogenic differentiation

Stančić

Drvenica

Bugarski

et al. 2020

ARCH BIOL SCI BELGRA

View full text Add to dashboard Cite

show abstract

“…Even though extracellular hemoglobin can be a part of the PB-MSC microenvironment, data in the literature regarding its influence on mesenchymal cells' migratory capacity are scarce. Bo et al [41] demonstrated that human glycated hemoglobin (HbA1c) inhibited the migration of HUVEC cells in a dose-and time-dependent manner [41]. Likewise, the peptides derived from bovine hemoglobin had the same effect on the MIAPaCa-2 cell line's migratory capacity [42].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Functional Characteristics of Mesenchymal Stromal Cells by Acellular Preparation of Porcine Hemoglobin

et al. 2021

View full text Add to dashboard Cite

Exploring the potential usage of the acellular preparation of porcine hemoglobin (PHb) isolated from slaughterhouse blood as a cell culture media component, we have tested its effects on the functional characteristics of stromal cells of mesodermal origin. Human peripheral blood mesenchymal stromal cells (PB-MSCs) were used in this study as a primary cell model system, along with three mouse cell lines (ATDC5, MC3T3-E1, and 3T3-L1), which represent more uniform model systems. We investigated the effect of PHb at concentrations of 0.1, 1, and 10 μM on these cells’ proliferation, cycle, and clonogenic and migratory potential, and found that PHb’s effect depended on both the cell type and its concentration. At the lowest concentration used (0.1 μM), PHb showed the least evident impact on the cell growth and migration; hence, we analyzed its effect on mesenchymal cell multilineage differentiation capacity at this concentration. Even under conditions that induce a specific type of MSC differentiation (cultivation in particular differentiation media), PHb modulated chondrogenic, osteogenic, and adipogenic differentiation, making it a potential candidate for a supplement of MSC culture. Through a model of porcine hemoglobin, these findings also contribute to improving the knowledge of extracellular hemoglobin’s influence on MSCs >in vivo.

show abstract

“…For example, one of the pathways presented in Figure 2 is HbA1c→NOS3→NAFLD. It has been shown that increased concentrations of HbA1c are capable of significantly down-regulating the expression of NOS3 [27]; resultant deficiency of NOS3 is a known contributor to NAFLD [28]. Another example is the HbA1c→ IL10→NAFLD pathway.…”

Section: Discussionmentioning

confidence: 99%

HbA1c may contribute to the development of non-alcoholic fatty liver disease even at normal-range levels

Chen¹,

Zhu²,

Mao

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

Previous clinical studies highlighted nonalcoholic fatty liver disease (NAFLD) as a hepatic facet of metabolic syndrome, which progresses toward Type 2 diabetes along with an elevation of HbA1c in the blood. Longitudinal observations were performed in a cohort of 2811 participants with no liver disease at inception. The rate of the conversion into NAFLD was 15.7% (440/2811), with a steady increase in prevalence observed in sub-cohorts with increasing HbA1c levels. Moreover, regression analysis indicated that HbA1c levels serve as the risk factors for NAFLD after multiple adjustments (odds ratio: 1.58, P-value < 0.004). When HbA1c-related molecular networks were investigated using natural language programming algorithms, multiple genetic/small molecular (SM) pathways were highlighted as connectors between the HbA1c levels and the development of NAFLD, including ones for nitric oxide, hypoxia and receptor for advanced glycation end products (RAGE). Our results suggest that increased levels of HbA1c may contribute to the progression of NAFLD either directly, by stimulating RAGE or indirectly, through the promotion of hypoxia and suppression of the release of NO. Further studies are needed to test the impact of HbA1c on the development of the chronic liver disease.

show abstract

Impairment of Endothelial Cell Function Induced by Hemoglobin A1c and the Potential Mechanisms

Abstract: These findings provide direct evidence that HbA(1c) is involved in the development and progression of the cardiovascular complications of diabetes.

Cited by 4 publications

References 20 publications

Extracellular xenogeneic hemoglobin suppresses the capacity for C2C12 myoblast myogenic differentiation

Extracellular xenogeneic hemoglobin suppresses the capacity for C2C12 myoblast myogenic differentiation

Modulation of Functional Characteristics of Mesenchymal Stromal Cells by Acellular Preparation of Porcine Hemoglobin

HbA1c may contribute to the development of non-alcoholic fatty liver disease even at normal-range levels

Contact Info

Product

Resources

About