Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extr... more Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes. Since the use of polyplexes for in vivo delivery is limited by their instability in the plasma and the non-specific tissue interactions, we designed and obtained targeted, lipid-enveloped polyplexes (lipopolyplexes) suitable for (1) systemic administration and (2) targeted delivery of shRunx2 to osteoblast-differentiated VIC (oVIC). Vascular cell adhesion molecule (VCAM)-1 expressed on the surface ...
Background MicroRNAs are involved in many processes such as cell proliferation and differentiatio... more Background MicroRNAs are involved in many processes such as cell proliferation and differentiation, angiogenesis, apoptosis, mitochondrial metabolism and DNA damage repair. Circulating levels of microRNA-210 (miR-210) are associated with the risk for cardiovascular mortality at patients with coronary artery disease. Purpose The aim was to investigate the effects and involved mechanisms of a novel treatment, miR-210 inhibitor (antagomiR-210), on the activation of inflammation and immune system, and overproduction of reactive oxygen species in atherosclerosis. Methods Golden Syrian hamsters were divided into: (1) simultaneously hypertensive - hyperlipidemic (HH) by combining two feeding conditions for 4 months, that mimic atherosclerosis; (2) HH with subcutaneous injection at months 1,2,3 containing antagomiR-210, or scramble (Scr)-miR negative control, or vehicle (phosphate-buffered saline, PBS) alone; (3) controls (C), age-matched normal healthy animals. Results The results showed t...
Hypertension (HT) is a major contributor to the dev elopment of renal failure, mainly due to incr... more Hypertension (HT) is a major contributor to the dev elopment of renal failure, mainly due to increased oxidative stress. The causative relations hip between raised blood pressure and overproduction of reactive oxygen species (ROS) is still controversial. Growing evidence attributes to NADP(H) oxidase the main role in ROS production in the renal cortex, while the angiotensin conversion enzyme (ACE) inhibitor, Zofenopril, is k nown to exert protective effects in kidney ischemia/reperfusion injury. In this study we appro ached understanding the biochemical background of imbalance between activation of pro-o xidant enzymes and decreased scavenging of ROS in HT, an issue with still many gaps in percept ion. With this goal we investigated the effects of Zofenopril on kidney cortex in an experimental m odel of N-Nitro-L-Arginine Methyl Ester (LNAME) induced HT in rats. Animals were divided in 3 groups: HT group (receiving orally 50mg/b.w./day L-NAME, for 6 weeks), HTZ group (HT, receiving ...
Experiments on hypercholesterolemic rabbits and hamsters (HH) showed that hyperlipemia induces in... more Experiments on hypercholesterolemic rabbits and hamsters (HH) showed that hyperlipemia induces initial activation of endothelial cells (EC) expressed by modulation of constitutive functions: increased transcytosis of low-density lipoproteins (LDL) and enhanced synthesis of basal lamina. Accumulated LDL appears in the meshes of basal lamina as modified and reassembled lipoproteins (MRL) that, together with hyperlipemia, triggers EC dysfunction. This induces monocyte
Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extr... more Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes. Since the use of polyplexes for in vivo delivery is limited by their instability in the plasma and the non-specific tissue interactions, we designed and obtained targeted, lipid-enveloped polyplexes (lipopolyplexes) suitable for (1) systemic administration and (2) targeted delivery of shRunx2 to osteoblast-differentiated VIC (oVIC). Vascular cell adhesion molecule (VCAM)-1 expressed on the surface ...
Background MicroRNAs are involved in many processes such as cell proliferation and differentiatio... more Background MicroRNAs are involved in many processes such as cell proliferation and differentiation, angiogenesis, apoptosis, mitochondrial metabolism and DNA damage repair. Circulating levels of microRNA-210 (miR-210) are associated with the risk for cardiovascular mortality at patients with coronary artery disease. Purpose The aim was to investigate the effects and involved mechanisms of a novel treatment, miR-210 inhibitor (antagomiR-210), on the activation of inflammation and immune system, and overproduction of reactive oxygen species in atherosclerosis. Methods Golden Syrian hamsters were divided into: (1) simultaneously hypertensive - hyperlipidemic (HH) by combining two feeding conditions for 4 months, that mimic atherosclerosis; (2) HH with subcutaneous injection at months 1,2,3 containing antagomiR-210, or scramble (Scr)-miR negative control, or vehicle (phosphate-buffered saline, PBS) alone; (3) controls (C), age-matched normal healthy animals. Results The results showed t...
Hypertension (HT) is a major contributor to the dev elopment of renal failure, mainly due to incr... more Hypertension (HT) is a major contributor to the dev elopment of renal failure, mainly due to increased oxidative stress. The causative relations hip between raised blood pressure and overproduction of reactive oxygen species (ROS) is still controversial. Growing evidence attributes to NADP(H) oxidase the main role in ROS production in the renal cortex, while the angiotensin conversion enzyme (ACE) inhibitor, Zofenopril, is k nown to exert protective effects in kidney ischemia/reperfusion injury. In this study we appro ached understanding the biochemical background of imbalance between activation of pro-o xidant enzymes and decreased scavenging of ROS in HT, an issue with still many gaps in percept ion. With this goal we investigated the effects of Zofenopril on kidney cortex in an experimental m odel of N-Nitro-L-Arginine Methyl Ester (LNAME) induced HT in rats. Animals were divided in 3 groups: HT group (receiving orally 50mg/b.w./day L-NAME, for 6 weeks), HTZ group (HT, receiving ...
Experiments on hypercholesterolemic rabbits and hamsters (HH) showed that hyperlipemia induces in... more Experiments on hypercholesterolemic rabbits and hamsters (HH) showed that hyperlipemia induces initial activation of endothelial cells (EC) expressed by modulation of constitutive functions: increased transcytosis of low-density lipoproteins (LDL) and enhanced synthesis of basal lamina. Accumulated LDL appears in the meshes of basal lamina as modified and reassembled lipoproteins (MRL) that, together with hyperlipemia, triggers EC dysfunction. This induces monocyte
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Papers by Gabriela Tanko