Publications by authors named "Tasnim Mohaissen"

6 Publications

  • Page 1 of 1

Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland.

Carbon monoxide (CO)-gaseous or released by CO-RMs-both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO-delivered by gaseous CO-saturated buffer (CO) and generated by CORM-A1-on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of CO on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, CO did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by CO or CORM-A1, was dependent on sGC. We conclude that the source (CO vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.
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http://dx.doi.org/10.3390/ijms22073584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037872PMC
March 2021

Spectroscopic Signature of Red Blood Cells in a D-Galactose-Induced Accelerated Aging Model.

Int J Mol Sci 2021 Mar 6;22(5). Epub 2021 Mar 6.

Jagiellonian Center for Experimental Therapeutics, Jagiellonian University, 14 Bobrzynskiego Str., 30-348 Krakow, Poland.

This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.
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http://dx.doi.org/10.3390/ijms22052660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961785PMC
March 2021

Age-related and atherosclerosis-related erythropathy in ApoE/LDLR mice.

Biochim Biophys Acta Mol Basis Dis 2020 12 17;1866(12):165972. Epub 2020 Sep 17.

Jagiellonian Center for Experimental Therapeutics, Jagiellonian University, 14 Bobrzyńskiego St., 30-348 Krakow, Poland. Electronic address:

In this work we applied a multimodal approach to define the age- and atherosclerosis-related biochemical and functional alterations in red blood cells (RBCs) in ApoE/LDLR mice. Our results revealed that age-related changes in RBCs, such as decreases in RBC deformability and mean height, were more pronounced in ApoE/LDLR mice than in age-matched control mice (C57BL/6J). The decreases in phospholipid content and level of lipid unsaturation were accompanied by an increase in cholesterol esters and esterified lipids in RBC membranes in aged C57BL/6J mice. The age-related decrease in the phospholipid content was more pronounced in ApoE/LDLR mice. In contrast, the increase in the total lipid content in RBC membranes occurred only in ApoE/LDLR mice with advanced atherosclerosis. The age-related alterations also included a decrease in the ratio of turns to α-helices in the secondary structure of hemoglobin (Hb) inside intact RBCs. On the other hand, an increase in the ratio of unordered conformations to α-helices of Hb was observed only in ApoE/LDLR mice and occurred already at the age of 5-weeks. This was related to hypercholesterolemia and resulted in an increased oxygen-carrying capacity. In conclusion, progressive mechanical and functional alterations of RBCs in aged ApoE/LDLR mice were more pronounced than in age-matched C57BL/6J mice. Although, several biochemical changes in RBCs in aged ApoE/LDLR mice recapitulated age-dependent changes observed in control mice, some biochemical features of RBC membranes attributed to hypercholesterolemia were distinct and could contribute to the accelerated deterioration of RBC function in ApoE/LDLR mice.
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http://dx.doi.org/10.1016/j.bbadis.2020.165972DOI Listing
December 2020

Nitric oxide deficiency and endothelial-mesenchymal transition of pulmonary endothelium in the progression of 4T1 metastatic breast cancer in mice.

Breast Cancer Res 2018 08 3;20(1):86. Epub 2018 Aug 3.

Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14 St., 30-348, Krakow, Poland.

Background: Mesenchymal transformation of pulmonary endothelial cells contributes to the formation of a metastatic microenvironment, but it is not known whether this precedes or follows early metastasis formation. In the present work, we characterize the development of nitric oxide (NO) deficiency and markers of endothelial-mesenchymal transition (EndMT) in the lung in relation to the progression of 4T1 metastatic breast cancer injected orthotopically in mice.

Methods: NO production, endothelial nitric oxide synthase (eNOS) phosphorylation status, markers of EndMT in the lung, pulmonary endothelium permeability, and platelet activation/reactivity were analyzed in relation to the progression of 4T1 breast cancer metastasis to the lung, as well as to lung tissue remodeling, 1-5 weeks after 4T1 cancer cell inoculation in Balb/c mice.

Results: Phosphorylation of eNOS and NO production in the lungs of 4T1 breast cancer-bearing mice was compromised prior to the development of pulmonary metastasis, and was associated with overexpression of Snail transcription factor in the pulmonary endothelium. These changes developed prior to the mesenchymal phenotypic switch in the lungs evidenced by a decrease in vascular endothelial-cadherin (VE-CAD) and CD31 expression, and the increase in pulmonary endothelial permeability, phenomena which coincided with early pulmonary metastasis. Increased activation of platelets was also detected prior to the early phase of metastasis and persisted to the late phase of metastasis, as evidenced by the higher percentage of unstimulated platelets binding fibrinogen without changes in von Willebrand factor and fibrinogen binding in response to ADP stimulation.

Conclusions: Decreased eNOS activity and phosphorylation resulting in a low NO production state featuring pulmonary endothelial dysfunction was an early event in breast cancer pulmonary metastasis, preceding the onset of its phenotypic switch toward a mesenchymal phenotype (EndMT) evidenced by a decrease in VE-CAD and CD31 expression. The latter coincided with development of the first metastatic nodules in the lungs. These findings suggest that early endothelial dysfunction featured by NO deficiency rather than EndMT, might represent a primary regulatory target to prevent early pulmonary metastasis.
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http://dx.doi.org/10.1186/s13058-018-1013-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091065PMC
August 2018

The Deletion of Endothelial Sodium Channel α (αENaC) Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia .

Front Pharmacol 2018 10;9:178. Epub 2018 Apr 10.

Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Kraków, Poland.

The role of epithelial sodium channel (ENaC) activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaC mice) using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from , 10 mg/kg, i.p.). In addition, changes in vascular permeability in organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaC vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaC vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by and analysis in endotoxemic endo-αENaC vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaC was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.
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http://dx.doi.org/10.3389/fphar.2018.00178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902527PMC
April 2018

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice.

J Am Heart Assoc 2018 03 26;7(7). Epub 2018 Mar 26.

Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland

Background: Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved.

Methods And Results: Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood-brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E-selectin immunoreactivity, which was accompanied by increased amyloid-β accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month-old Tgαq*44 mice, but it was not associated with increased platelet-dependent thrombogenicity.

Conclusions: We report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation.
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http://dx.doi.org/10.1161/JAHA.117.007694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907583PMC
March 2018