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Article: Biofunctionalization of cardiovascular stents to induce endothelialization: Implications for in- stent thrombosis in diabetes.

Marei, Isra / Ahmetaj-Shala, Blerina / Triggle, Chris R

2022 Volume 13, Page(s) 982185

Abstract: Stent thrombosis remains one of the main causes that lead to vascular stent failure in patients undergoing percutaneous coronary intervention (PCI). Type 2 diabetes mellitus is accompanied by endothelial dysfunction and platelet hyperactivity and is ... ...

Abstract	Stent thrombosis remains one of the main causes that lead to vascular stent failure in patients undergoing percutaneous coronary intervention (PCI). Type 2 diabetes mellitus is accompanied by endothelial dysfunction and platelet hyperactivity and is associated with suboptimal outcomes following PCI, and an increase in the incidence of late stent thrombosis. Evidence suggests that late stent thrombosis is caused by the delayed and impaired endothelialization of the lumen of the stent. The endothelium has a key role in modulating inflammation and thrombosis and maintaining homeostasis, thus restoring a functional endothelial cell layer is an important target for the prevention of stent thrombosis. Modifications using specific molecules to induce endothelial cell adhesion, proliferation and function can improve stents endothelialization and prevent thrombosis. Blood endothelial progenitor cells (EPCs) represent a potential cell source for the in situ-endothelialization of vascular conduits and stents. We aim in this review to summarize the main biofunctionalization strategies to induce the
Language	English
Publishing date	2022-10-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.982185
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Article ; Online: Relationship of anti-SARS-CoV-2 IgG antibodies with Vitamin D and inflammatory markers in COVID-19 patients.

Latifi-Pupovci, Hatixhe / Namani, Sadie / Pajaziti, Artina / Ahmetaj-Shala, Blerina / Ajazaj, Lindita / Kotori, Afrim / Haxhibeqiri, Valdete / Gegaj, Valentin / Bunjaku, Gramoz

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5699

Abstract: Several studies have found an association of COVID-19 disease severity with Vitamin D deficiency and higher levels of anti-SARS-CoV-2 IgGs. The aim of this study was to determine whether levels of Vitamin D and "inflammatory state" influence the ... ...

Abstract	Several studies have found an association of COVID-19 disease severity with Vitamin D deficiency and higher levels of anti-SARS-CoV-2 IgGs. The aim of this study was to determine whether levels of Vitamin D and "inflammatory state" influence the magnitude of anti-SARS-CoV-2 IgGs levels in COVID-19 patients. For this purpose, in 67 patients levels of anti-SARS-CoV-2 IgG were measured in week 4 whereas in 52 patients levels of Vitamin D were measured in week 1 after symptom onset. We found that low Vitamin D levels were significantly associated with age and disease severity whereas there was a trend without significance, towards negative correlation of Vitamin D with anti-SARS-CoV-2 IgG. Anti-SARS-CoV-2 IgG were significantly higher in older ages, patients with severe disease, diabetes and those who received corticosteroid and antibiotic therapy. There was a positive correlation of anti-SARS-CoV-2 IgG with IL-6, CRP, LDH, ESR and with percentages of granulocytes. In conclusion, Vitamin D and anti-SARS-CoV-2 IgG share common parameters associated with inflammatory state. However, even though Vitamin D protects against severe forms of COVID-19 it could not directly affect anti-SARS-CoV-2 IgG production.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; Humans ; Immunoglobulin G ; SARS-CoV-2 ; Vitamin D
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Vitamin D (1406-16-2)
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09785-7
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Article: Biomarkers of Inflammation among Patients with COVID-19: A Single-Centre Prospective Study from Prishtina, Kosovo.

Latifi-Pupovci, Hatixhe / Namani, Sadie / Ahmetaj-Shala, Blerina / Pajaziti, Artina / Bunjaku, Gramoz / Ajazaj Berisha, Lindita / Gegaj, Valentin / Kotori, Afrim

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale

2022 Volume 2022, Page(s) 4461647

Abstract: SARS-CoV-2 infection involves the phase of viral replication and inflammatory response predicting the severity of COVID-19. The aim of the study was to analyze the association between IL-6 and hematological and inflammatory parameters and outcomes of ... ...

Abstract	SARS-CoV-2 infection involves the phase of viral replication and inflammatory response predicting the severity of COVID-19. The aim of the study was to analyze the association between IL-6 and hematological and inflammatory parameters and outcomes of patients with COVID-19. Plasma interleukin 6 (IL-6) levels and other inflammatory and hematological parameters were analyzed in 86 adult patients diagnosed with SARS-CoV-2 infection in Kosovo. The median age of patients was 61.50 (49.75-67.25) years. Over half of patients were categorised as severe (58%) and had comorbidities (69%) with hypertension being the most common. The overall mortality rate was 4.7%. The distribution of biochemical parameters across disease severity groups was significantly different for C-reactive protein (CRP), lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), white blood cells (WBC), and granulocytes with higher median values in more severe and critically ill patients whereas lower percentage of lymphocytes, monocytes, and platelet count in severe and critically ill patients. IL-6 levels were increased in 63% of patients with significant differences in the distribution across the following groups; age, disease severity, hospitalisation status, pulmonary infiltrates, oxygen therapy, and hypertension status. IL-6 significantly correlated with CRP, LDH, CK, ESR, and percentages of granulocytes. IL-6 and other inflammatory and hematological parameters were strongly associated with disease severity and may predict the outcome of the SARS-CoV-2 infection.
Language	English
Publishing date	2022-07-15
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	1057056-1
ISSN	1712-9532 ; 1180-2332
ISSN	1712-9532 ; 1180-2332
DOI	10.1155/2022/4461647
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Article ; Online: Incidence of haematological malignancies in Kosovo-A post "uranium war" concern.

Latifi-Pupovci, Hatixhe / Selmonaj, Miranda / Ahmetaj-Shala, Blerina / Dushi, Mimoza / Grajqevci, Violeta

PloS one

2020 Volume 15, Issue 5, Page(s) e0232063

Abstract: Background: During the Kosovo War (1998-99) approximately 31,000 rounds with Depleted Uranium (DU) were fired on 85 targets in Kosovo. The number of haematological malignancies (HM) increased after the war and the concern was the use of DU during the ... ...

Abstract	Background: During the Kosovo War (1998-99) approximately 31,000 rounds with Depleted Uranium (DU) were fired on 85 targets in Kosovo. The number of haematological malignancies (HM) increased after the war and the concern was the use of DU during the war. The aim of this study was to analyse the incidence rates of HM in Kosovo throughout a 20-year that includes pre- and post- war period (1995-2015); and to examine if there is any association between the use of DU rounds and incidence rates of HM in different regions of Kosovo. Methods: In this retrospective register-based study, 1,798 new patients diagnosed with leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and Multiple myeloma were analysed over a 20 year period. Incidence rates were calculated focusing on specific time periods, regions and age-groups. In addition, the correlation between the use of DU in different regions and their incidence of HM was analysed. Results: The average annual crude rate of all HM in Kosovo was 5.02 cases per 100,000 persons. Incidence rates of HM in first post-war period (2000-2003) increased by 0.37 cases/100,000 persons (9.51%) compared to the pre-war period (1995-1998) whereas in the last post-war period (2012-2015), incidence of HM increased by 3.19/100,000 persons (82%). Gjakova and Peja, the first and third most exposed regions to DU ordnance ranked first and second in difference in HM. Prishtina, Gjilan and Ferizaj, regions with the least number of rounds/km2, were characterized by a decline of incidence rates. Conclusions: After the war, the increase in incidence rate of HM was higher in two regions with most DU rounds/km2 expended Despite these findings, this study warrants further investigation and does not lead us to a conclusive finding on the existence of a causal relationship between the use of DU during the war and the rise in incidence of HM in Kosovo.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Hematologic Neoplasms/epidemiology ; Hematologic Neoplasms/history ; History, 20th Century ; History, 21st Century ; Humans ; Incidence ; Infant ; Infant, Newborn ; Kosovo/epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Uranium ; Warfare/history ; Young Adult
Chemical Substances	Uranium (4OC371KSTK)
Language	English
Publishing date	2020-05-04
Publishing country	United States
Document type	Historical Article ; Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0232063
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Article ; Online: Widening the Prostacyclin Paradigm: Tissue Fibroblasts Are a Critical Site of Production and Antithrombotic Protection.

Vinokurova, Maria / Lopes-Pires, Maria Elisa / Cypaite, Neringa / Shala, Fisnik / Armstrong, Paul C / Ahmetaj-Shala, Blerina / Elghazouli, Youssef / Nüsing, Rolf / Liu, Bin / Zhou, Yingbi / Hao, Chuan-Ming / Herschman, Harvey R / Mitchell, Jane A / Kirkby, Nicholas S

Arteriosclerosis, thrombosis, and vascular biology

2023 Volume 44, Issue 1, Page(s) 271–286

Abstract: Background: Prostacyclin is a fundamental signaling pathway traditionally associated with the cardiovascular system and protection against thrombosis but which also has regulatory functions in fibrosis, proliferation, and immunity. Prevailing dogma ... ...

Abstract	Background: Prostacyclin is a fundamental signaling pathway traditionally associated with the cardiovascular system and protection against thrombosis but which also has regulatory functions in fibrosis, proliferation, and immunity. Prevailing dogma states that prostacyclin is principally derived from vascular endothelium, although it is known that other cells can also synthesize it. However, the role of nonendothelial sources in prostacyclin production has not been systematically evaluated resulting in an underappreciation of their importance relative to better characterized endothelial sources. Methods: To address this, we have used novel endothelial cell-specific and fibroblast-specific COX (cyclo-oxygenase) and prostacyclin synthase knockout mice and cells freshly isolated from mouse and human lung tissue. We have assessed prostacyclin release by immunoassay and thrombosis in vivo using an FeCl Results: We found that in arteries, endothelial cells are the main source of prostacyclin but that in the lung, and other tissues, prostacyclin production occurs largely independently of endothelial and vascular smooth muscle cells. Instead, in mouse and human lung, prostacyclin production was strongly associated with fibroblasts. By comparison, microvascular endothelial cells from the lung showed weak prostacyclin synthetic capacity compared with those isolated from large arteries. Prostacyclin derived from fibroblasts and other nonendothelial sources was seen to contribute to antithrombotic protection. Conclusions: These observations define a new paradigm in prostacyclin biology in which fibroblast/nonendothelial-derived prostacyclin works in parallel with endothelium-derived prostanoids to control thrombotic risk and potentially a broad range of other biology. Although generation of prostacyclin by fibroblasts has been shown previously, the scale and systemic activity was unappreciated. As such, this represents a basic change in our understanding and may provide new insight into how diseases of the lung result in cardiovascular risk.
MeSH term(s)	Mice ; Humans ; Animals ; Epoprostenol ; Fibrinolytic Agents ; Endothelial Cells/metabolism ; Prostaglandins I/metabolism ; Prostaglandins I/pharmacology ; Endothelium, Vascular/metabolism ; Mice, Knockout ; Fibroblasts/metabolism ; Thrombosis/genetics ; Thrombosis/prevention & control ; Thrombosis/metabolism
Chemical Substances	Epoprostenol (DCR9Z582X0) ; Fibrinolytic Agents ; Prostaglandins I
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.318923
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Zs.A 1705: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: Relationship of anti-SARS-CoV-2 IgG antibodies with Vitamin D and inflammatory markers in COVID-19 patients

Hatixhe Latifi-Pupovci / Sadie Namani / Artina Pajaziti / Blerina Ahmetaj-Shala / Lindita Ajazaj / Afrim Kotori / Valdete Haxhibeqiri / Valentin Gegaj / Gramoz Bunjaku

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 9

Abstract: Abstract Several studies have found an association of COVID-19 disease severity with Vitamin D deficiency and higher levels of anti-SARS-CoV-2 IgGs. The aim of this study was to determine whether levels of Vitamin D and “inflammatory state” influence the ...

Abstract	Abstract Several studies have found an association of COVID-19 disease severity with Vitamin D deficiency and higher levels of anti-SARS-CoV-2 IgGs. The aim of this study was to determine whether levels of Vitamin D and “inflammatory state” influence the magnitude of anti-SARS-CoV-2 IgGs levels in COVID-19 patients. For this purpose, in 67 patients levels of anti-SARS-CoV-2 IgG were measured in week 4 whereas in 52 patients levels of Vitamin D were measured in week 1 after symptom onset. We found that low Vitamin D levels were significantly associated with age and disease severity whereas there was a trend without significance, towards negative correlation of Vitamin D with anti-SARS-CoV-2 IgG. Anti-SARS-CoV-2 IgG were significantly higher in older ages, patients with severe disease, diabetes and those who received corticosteroid and antibiotic therapy. There was a positive correlation of anti-SARS-CoV-2 IgG with IL-6, CRP, LDH, ESR and with percentages of granulocytes. In conclusion, Vitamin D and anti-SARS-CoV-2 IgG share common parameters associated with inflammatory state. However, even though Vitamin D protects against severe forms of COVID-19 it could not directly affect anti-SARS-CoV-2 IgG production.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cardiorenal Tissues Express SARS-CoV-2 Entry Genes and Basigin (BSG/CD147) Increases With Age in Endothelial Cells.

Ahmetaj-Shala, Blerina / Vaja, Ricky / Atanur, Santosh S / George, Peter M / Kirkby, Nicholas S / Mitchell, Jane A

JACC. Basic to translational science

2020 Volume 5, Issue 11, Page(s) 1111–1123

Abstract: Vascular and cardiovascular inflammation and thrombosis occur in patients with severe coronavirus disease-2019 (COVID-19). Advancing age is the most significant risk factor for severe COVID-19. Using transcriptomic databases, the authors found that: 1) ... ...

Abstract	Vascular and cardiovascular inflammation and thrombosis occur in patients with severe coronavirus disease-2019 (COVID-19). Advancing age is the most significant risk factor for severe COVID-19. Using transcriptomic databases, the authors found that: 1) cardiovascular tissues and endothelial cells express putative genes for severe acute respiratory syndrome coronavirus-2 infection, including angiotensin-converting enzyme 2 (
Keywords	covid19
Language	English
Publishing date	2020-10-09
Publishing country	United States
Document type	Journal Article
ISSN	2452-302X
ISSN (online)	2452-302X
DOI	10.1016/j.jacbts.2020.09.010
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Article ; Online: Incidence of haematological malignancies in Kosovo-A post "uranium war" concern.

Hatixhe Latifi-Pupovci / Miranda Selmonaj / Blerina Ahmetaj-Shala / Mimoza Dushi / Violeta Grajqevci

PLoS ONE, Vol 15, Iss 5, p e

2020 Volume 0232063

Abstract: BACKGROUND:During the Kosovo War (1998-99) approximately 31,000 rounds with Depleted Uranium (DU) were fired on 85 targets in Kosovo. The number of haematological malignancies (HM) increased after the war and the concern was the use of DU during the war. ...

Abstract	BACKGROUND:During the Kosovo War (1998-99) approximately 31,000 rounds with Depleted Uranium (DU) were fired on 85 targets in Kosovo. The number of haematological malignancies (HM) increased after the war and the concern was the use of DU during the war. The aim of this study was to analyse the incidence rates of HM in Kosovo throughout a 20-year that includes pre- and post- war period (1995-2015); and to examine if there is any association between the use of DU rounds and incidence rates of HM in different regions of Kosovo. METHODS:In this retrospective register-based study, 1,798 new patients diagnosed with leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and Multiple myeloma were analysed over a 20 year period. Incidence rates were calculated focusing on specific time periods, regions and age-groups. In addition, the correlation between the use of DU in different regions and their incidence of HM was analysed. RESULTS:The average annual crude rate of all HM in Kosovo was 5.02 cases per 100,000 persons. Incidence rates of HM in first post-war period (2000-2003) increased by 0.37 cases/100,000 persons (9.51%) compared to the pre-war period (1995-1998) whereas in the last post-war period (2012-2015), incidence of HM increased by 3.19/100,000 persons (82%). Gjakova and Peja, the first and third most exposed regions to DU ordnance ranked first and second in difference in HM. Prishtina, Gjilan and Ferizaj, regions with the least number of rounds/km2, were characterized by a decline of incidence rates. CONCLUSIONS:After the war, the increase in incidence rate of HM was higher in two regions with most DU rounds/km2 expended Despite these findings, this study warrants further investigation and does not lead us to a conclusive finding on the existence of a causal relationship between the use of DU during the war and the rise in incidence of HM in Kosovo.
Keywords	Medicine ; R ; Science ; Q
Subject code	940
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Activation and Contraction of Human "Vascular" Smooth Muscle Cells Grown From Circulating Blood Progenitors.

Ahmetaj-Shala, Blerina / Marei, Isra / Kawai, Ryota / Rothery, Stephen / Pericleous, Charis / Mohamed, Nura A / Gashaw, Hime / Bokea, Kalliopi / Samuel, Jake / Vandenheste, Annabelle / Shala, Fisnik / Kirkby, Nicholas S / Mitchell, Jane A

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 681347

Abstract: Blood outgrowth smooth muscle cells (BO-SMCs) offer the means to study vascular cells without the requirement for surgery providing opportunities for drug discovery, tissue engineering, and personalized medicine. However, little is known about these ... ...

Abstract	Blood outgrowth smooth muscle cells (BO-SMCs) offer the means to study vascular cells without the requirement for surgery providing opportunities for drug discovery, tissue engineering, and personalized medicine. However, little is known about these cells which meant that their therapeutic potential remains unexplored. Our objective was to investigate for the first time the ability of BO-SMCs and vessel-derived smooth muscle cells to sense the thromboxane mimetic U46619 by measuring intracellular calcium elevation and contraction. U46619 (10
Language	English
Publishing date	2021-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.681347
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Article ; Online: Studies on metal-organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension.

Mohamed, Nura A / Abou-Saleh, Haissam / Kameno, Yu / Marei, Isra / de Nucci, Gilberto / Ahmetaj-Shala, Blerina / Shala, Fisnik / Kirkby, Nicholas S / Jennings, Lewis / Al-Ansari, Dana E / Davies, Robert P / Lickiss, Paul D / Mitchell, Jane A

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4336

Abstract: Pulmonary arterial hypertension (PAH) is an incurable disease, although symptoms are treated with a range of dilator drugs. Despite their clinical benefits, these drugs are limited by systemic side-effects. It is, therefore, increasingly recognised that ... ...

Abstract	Pulmonary arterial hypertension (PAH) is an incurable disease, although symptoms are treated with a range of dilator drugs. Despite their clinical benefits, these drugs are limited by systemic side-effects. It is, therefore, increasingly recognised that using controlled drug-release nanoformulation, with future modifications for targeted drug delivery, may overcome these limitations. This study presents the first evaluation of a promising nanoformulation (highly porous iron-based metal-organic framework (MOF); nanoMIL-89) as a carrier for the PAH-drug sildenafil, which we have previously shown to be relatively non-toxic in vitro and well-tolerated in vivo. In this study, nanoMIL-89 was prepared and charged with a payload of sildenafil (generating Sil@nanoMIL-89). Sildenafil release was measured by Enzyme-Linked Immunosorbent Assay (ELISA), and its effect on cell viability and dilator function in mouse aorta were assessed. Results showed that Sil@nanoMIL-89 released sildenafil over 6 h, followed by a more sustained release over 72 h. Sil@nanoMIL-89 showed no significant toxicity in human blood outgrowth endothelial cells for concentrations up to100µg/ml; however, it reduced the viability of the human pulmonary artery smooth muscle cells (HPASMCs) at concentrations > 3 µg/ml without inducing cellular cytotoxicity. Finally, Sil@nanoMIL-89 induced vasodilation of mouse aorta after a lag phase of 2-4 h. To our knowledge, this study represents the first demonstration of a novel nanoformulation displaying delayed drug release corresponding to vasodilator activity. Further pharmacological assessment of our nanoformulation, including in PAH models, is required and constitutes the subject of ongoing investigations.
MeSH term(s)	Animals ; Aorta/drug effects ; Cell Survival/drug effects ; Drug Liberation ; Humans ; Kinetics ; Metal-Organic Frameworks/chemistry ; Metal-Organic Frameworks/ultrastructure ; Mice ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Phosphodiesterase 5 Inhibitors/administration & dosage ; Phosphodiesterase 5 Inhibitors/chemistry ; Phosphodiesterase 5 Inhibitors/pharmacokinetics ; Pulmonary Arterial Hypertension/drug therapy ; Pulmonary Arterial Hypertension/etiology ; Sildenafil Citrate/administration & dosage ; Sildenafil Citrate/chemistry ; Sildenafil Citrate/pharmacokinetics ; Spectrum Analysis ; Theranostic Nanomedicine ; Vasodilator Agents/administration & dosage ; Vasodilator Agents/chemistry ; Vasodilator Agents/pharmacokinetics
Chemical Substances	Metal-Organic Frameworks ; Phosphodiesterase 5 Inhibitors ; Vasodilator Agents ; Sildenafil Citrate (BW9B0ZE037)
Language	English
Publishing date	2021-02-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-83423-6
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