TY  - JOUR
AU  - Popović, Milan
AU  - Smiljanić, Katarina
AU  - Dobutović, Branislava
AU  - Syrovets, Tatiana
AU  - Simmet, Thomas
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4578
AB  - Vascular endothelium is a key regulator of homeostasis. In physiological conditions it mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. However, endothelial dysfunction caused by physical injury of the vascular wall, for example during balloon angioplasty, acute or chronic inflammation, such as in atherothrombosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites. At the same time, the dysfunction promotes thrombin generation, fibrin deposition, and coagulation. The serine protease thrombin plays a pivotal role in the coagulation cascade. However, thrombin is not only the key effector of coagulation cascade; it also plays a significant role in inflammatory diseases. It shows an array of effects on endothelial cells, vascular smooth muscle cells, monocytes, and platelets, all of which participate in the vascular pathophysiology such as atherothrombosis. Therefore, thrombin can be considered as an important modulatory molecule of vascular homeostasis. This review summarizes the existing evidence on the role of thrombin in vascular inflammation.
T2  - Molecular and Cellular Biochemistry
T1  - Thrombin and vascular inflammation
VL  - 359
IS  - 1-2
SP  - 301
EP  - 313
DO  - 10.1007/s11010-011-1024-x
ER  - 

@article{
author = "Popović, Milan and Smiljanić, Katarina and Dobutović, Branislava and Syrovets, Tatiana and Simmet, Thomas and Isenović, Esma R.",
year = "2012",
abstract = "Vascular endothelium is a key regulator of homeostasis. In physiological conditions it mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. However, endothelial dysfunction caused by physical injury of the vascular wall, for example during balloon angioplasty, acute or chronic inflammation, such as in atherothrombosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites. At the same time, the dysfunction promotes thrombin generation, fibrin deposition, and coagulation. The serine protease thrombin plays a pivotal role in the coagulation cascade. However, thrombin is not only the key effector of coagulation cascade; it also plays a significant role in inflammatory diseases. It shows an array of effects on endothelial cells, vascular smooth muscle cells, monocytes, and platelets, all of which participate in the vascular pathophysiology such as atherothrombosis. Therefore, thrombin can be considered as an important modulatory molecule of vascular homeostasis. This review summarizes the existing evidence on the role of thrombin in vascular inflammation.",
journal = "Molecular and Cellular Biochemistry",
title = "Thrombin and vascular inflammation",
volume = "359",
number = "1-2",
pages = "301-313",
doi = "10.1007/s11010-011-1024-x"
}

Popović, M., Smiljanić, K., Dobutović, B., Syrovets, T., Simmet, T.,& Isenović, E. R.. (2012). Thrombin and vascular inflammation. in Molecular and Cellular Biochemistry, 359(1-2), 301-313.
https://doi.org/10.1007/s11010-011-1024-x

Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenović ER. Thrombin and vascular inflammation. in Molecular and Cellular Biochemistry. 2012;359(1-2):301-313.
doi:10.1007/s11010-011-1024-x .

Popović, Milan, Smiljanić, Katarina, Dobutović, Branislava, Syrovets, Tatiana, Simmet, Thomas, Isenović, Esma R., "Thrombin and vascular inflammation" in Molecular and Cellular Biochemistry, 359, no. 1-2 (2012):301-313,
https://doi.org/10.1007/s11010-011-1024-x . .

TY  - JOUR
AU  - Popović, Milan
AU  - Smiljanić, Katarina
AU  - Dobutović, Branislava
AU  - Syrovets, Tatiana
AU  - Simmet, Thomas
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4670
AB  - Vascular endothelium, as a key regulator of hemostasis, mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. Endothelial dysfunction caused by acute or chronic inflammation, such as in atherosclerosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites, and at the same time promotes coagulation, thrombin generation, and fibrin deposition in an attempt to close the wound. Life-long persistent infection with human cytomegalovirus (HCMV) has been associated with atherosclerosis. In vivo studies have revealed that HCMV infection of the vessel wall affects various cells including monocytes/macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs). HCMV-infected SMCs within vascular lesions display enhanced proliferation and impaired apoptosis, which contribute to intima-media thickening, plaque formation and restenosis. Monocytes play a central role in the process of viral dissemination, whereas ECs may represent a viral reservoir, maintaining persistent infection in HCMV-infected atherosclerotic patients following the primary infection. Persistent infection leads to dysfunction of ECs and activates proinflammatory signaling involving nuclear factor kappa B, specificity protein 1, and phosphatidylinositol 3-kinase, as well as expression of platelet-derived growth factor receptor. Activation of these pathways promotes enhanced proliferation and migration of monocytes and SMCs into the intima of the vascular wall as well as lipid accumulation and expansion of the atherosclerotic lesion. Moreover, HCMV infection induces enhanced expression of endothelial adhesion molecules and modifies the proteolytic balance in monocytes and macrophages. As a consequence, infected endothelium recruits naive monocytes from the blood stream, and the concomitant interaction between infected ECs and monocytes enables virus transfer to migrating monocytes. Endothelial damage promotes thrombin generation linking inflammation and coagulation. HCMV, in turn, enhances the thrombin generation. The virus carries on its surface the molecular machinery necessary to initiate thrombin generation, and in addition, may interact with the prothrombinase protein complex thereby facilitating thrombin generation. Thus, infection of endothelium may significantly increase the production of thrombin. This might not only contribute to thrombosis in patients with atherosclerosis, but might also induce thrombin-dependent proinflammatory cell activation. This review summarizes the existing evidence on the role of HCMV in vascular inflammation.
T2  - Journal of Thrombosis and Thrombolysis
T1  - Human cytomegalovirus infection and atherothrombosis
VL  - 33
IS  - 2
SP  - 160
EP  - 172
DO  - 10.1007/s11239-011-0662-x
ER  - 

@article{
author = "Popović, Milan and Smiljanić, Katarina and Dobutović, Branislava and Syrovets, Tatiana and Simmet, Thomas and Isenović, Esma R.",
year = "2012",
abstract = "Vascular endothelium, as a key regulator of hemostasis, mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. Endothelial dysfunction caused by acute or chronic inflammation, such as in atherosclerosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites, and at the same time promotes coagulation, thrombin generation, and fibrin deposition in an attempt to close the wound. Life-long persistent infection with human cytomegalovirus (HCMV) has been associated with atherosclerosis. In vivo studies have revealed that HCMV infection of the vessel wall affects various cells including monocytes/macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs). HCMV-infected SMCs within vascular lesions display enhanced proliferation and impaired apoptosis, which contribute to intima-media thickening, plaque formation and restenosis. Monocytes play a central role in the process of viral dissemination, whereas ECs may represent a viral reservoir, maintaining persistent infection in HCMV-infected atherosclerotic patients following the primary infection. Persistent infection leads to dysfunction of ECs and activates proinflammatory signaling involving nuclear factor kappa B, specificity protein 1, and phosphatidylinositol 3-kinase, as well as expression of platelet-derived growth factor receptor. Activation of these pathways promotes enhanced proliferation and migration of monocytes and SMCs into the intima of the vascular wall as well as lipid accumulation and expansion of the atherosclerotic lesion. Moreover, HCMV infection induces enhanced expression of endothelial adhesion molecules and modifies the proteolytic balance in monocytes and macrophages. As a consequence, infected endothelium recruits naive monocytes from the blood stream, and the concomitant interaction between infected ECs and monocytes enables virus transfer to migrating monocytes. Endothelial damage promotes thrombin generation linking inflammation and coagulation. HCMV, in turn, enhances the thrombin generation. The virus carries on its surface the molecular machinery necessary to initiate thrombin generation, and in addition, may interact with the prothrombinase protein complex thereby facilitating thrombin generation. Thus, infection of endothelium may significantly increase the production of thrombin. This might not only contribute to thrombosis in patients with atherosclerosis, but might also induce thrombin-dependent proinflammatory cell activation. This review summarizes the existing evidence on the role of HCMV in vascular inflammation.",
journal = "Journal of Thrombosis and Thrombolysis",
title = "Human cytomegalovirus infection and atherothrombosis",
volume = "33",
number = "2",
pages = "160-172",
doi = "10.1007/s11239-011-0662-x"
}

Popović, M., Smiljanić, K., Dobutović, B., Syrovets, T., Simmet, T.,& Isenović, E. R.. (2012). Human cytomegalovirus infection and atherothrombosis. in Journal of Thrombosis and Thrombolysis, 33(2), 160-172.
https://doi.org/10.1007/s11239-011-0662-x

Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenović ER. Human cytomegalovirus infection and atherothrombosis. in Journal of Thrombosis and Thrombolysis. 2012;33(2):160-172.
doi:10.1007/s11239-011-0662-x .

Popović, Milan, Smiljanić, Katarina, Dobutović, Branislava, Syrovets, Tatiana, Simmet, Thomas, Isenović, Esma R., "Human cytomegalovirus infection and atherothrombosis" in Journal of Thrombosis and Thrombolysis, 33, no. 2 (2012):160-172,
https://doi.org/10.1007/s11239-011-0662-x . .