Browsing by Author "Hofmanis, Juris"
Now showing 1 - 8 of 8
Results Per Page
Sort Options
Item HDL-C role in acquired aortic valve stenosis patients and its relationship with oxidative stress(2019-08) Hofmanis, Juris; Hofmane, Dace; Svirskis, Simons; Mackevics, Vitolds; Tretjakovs, Peteris; Lejnieks, Aivars; Signorelli, Salvatore Santo; Department of Internal Diseases; Institute of Microbiology and Virology; Department of Human Physiology and BiochemistryBackground and objectives: Mechanical stress is currently considered as the main factor promoting calcific aortic valve stenosis (AS) onset. It causes endothelial damage and dysfunction. The chronic inflammatory process causes oxidative stress. Oxidative stress-induced high-density lipoprotein cholesterol (HDL-C) dysfunction is an important component of the development of AS. The aim of the study was to evaluate the role of HDL-C in AS patients in three severity grades and in relation to the biomarkers of oxidative stress, thioredoxin reductase 1 (TrxR1) and myeloperoxidase (MPO). Materials and Methods: 18 patients with mild, 19 with moderate. and 15 with severe AS were included in the study, and 50 individuals were enrolled in the control group. Stenosis severity was determined by echocardiography. The TrxR1 and MPO were analyzed by ELISA, and HDL-C by commercially available tests. Data were analyzed using GraphPad Prism 8. Results: HDL-C in AS patients vs. control substantially decreases and this decline was observed in all three AS severity groups: mild (p = 0.018), moderate (p = 0.0002), and severe (p = 0.004). In both the control and the stenosis group, the HDL-C was higher in women than in men. In comparison to control, the HDL-C level was lower in the AS group, and more pronounced in women (p = 0.0001) than in men (p = 0.049). A higher TrxR1 level was observed in patients with mild (p = 0.0001) and severe AS (p = 0.047). However, a clear correlation between TrxR1 and HDL-C was not obtained. Analysis of MPO showed differences in all severity grades vs. control (p = 0.024 mild stenosis; p = 0.002 moderate stenosis; p = 0.0015 severe stenosis). A negative correlation (p = 0.047; rp = −0.28) was found between MPO and HDL-C, which confirms the adverse effects of MPO resulting in HDL-C dysfunction. Conclusions: In this study, we justified HDL-C level association with AS development process. The results unequivocally substantiated the association between HDL-C and AS in all severity grades in women, but only in moderate AS for men, which we explained by the small number of men in the groups. The obtained correlation between the HDL-C and MPO levels, as well as the concurrent decrease in the HDL-C level and increase in the TrxR1 level, indicate in general an HDL-C association with oxidative stress in AS patients.Item Iekaisīgie un neiekaisīgie riska faktori iegūtas aortas vārstuļa stenozes gadījumā. Promocijas darba kopsavilkums(Rīgas Stradiņa universitāte, 2019) Hofmanis, Juris; Mackēvičs, Vitolds; Tretjakovs, PēterisKalcificējoša aortas vārstuļa stenoze (AVS) izpaužas ar aortas vārstuļa (AV) viru fibro-kalcinējošu remodelāciju (pārveidošanos), kas ir lēni noritošs hroniska iekaisuma un kalcifikācijas process ar pilnībā neizzinātu un neviennozīmīgu etioloģiju un patoģenēzi. Pašlaik nav medikamentozas ārstēšanas, lai apturētu vai aizkavētu slimības progresēšanu. Vienīgā pieejamā ārstēšana ir ķirurģiska un AV nomaiņa vai transkatetrāla aortas vārstuļa implantācija. Pieaugot cilvēku dzīvildzei, pieaug to pacientu skaits, kuriem ir klīniski nozīmīga AVS. Gandrīz 25% cilvēku pēc 65 gadu vecuma ehokardiogrāfiski atrod AV sklerozi un apmēram 17% no šiem cilvēkiem turpmāk attīstās AVS. Laiks no AV sklerozes diagnosticēšanas līdz smagas AVS attīstībai vidēji ir 6–8 gadi. Pētnieciskā darba mērķis ir analizēt un noskaidrot, kuri no iekaisuma un kalcifikācijas procesā iesaistītajiem faktoriem, šūnu producētajām regulējošajām molekulām (citokīniem) un cik lielā mērā ietekmē AVS attīstību visās trīs AVS smaguma pakāpēs. Rezultātā varētu izdalīt kādu biomarķieri, ar kura palīdzību būtu iespējams prognozēt AVS progresēšanas ātrumu. Šūnu producētās regulējošās molekulas (citokīni) tika noteikti asins serumā un plazmā (tioredoksīna reduktāze-1, mieloperoksidāze). Pētnieciskā darba gaitā tika analizēta oksidatīvā stresa un iekaisuma mijiedarbība visās trijās AVS pakāpēs. Tāpat vēlreiz tika izvērtēta kopējā holesterīna un tā frakciju tieša un netieša ietekme uz AVS attīstību. Veiktais klīniski–analītiskais pētījums ir jaukta tipa prospektīvs gadījuma – kontroles pētījums. Brīvprātīgi tika atlasīti 102 pacienti, vadoties pēc iekļaušanas uz izslēgšanas kritērijiem un iedalīti divās pamatgrupās: kontroles grupā un AV stenozes grupā. Indivīdi kontroles grupā tika iekļauti atbilstoši ehokardiogrāfiski apstiprinātam veselam aortas vārstulim vecumā no 50 līdz 80 gadiem, kas atbilst AV stenozes pacientu vecumam, vadoties pēc 2012. gada Eiropas Kardiologu biedrības un Eiropas Sirds un Torakālo Ķirurgu asociācijas darba grupas sirds vārstuļu slimību ārstēšanas vadlīnijām. AV stenozes grupas pacienti tika sadalīti trīs apakšgrupās, atbilstoši AV stenozes pakāpei, vadoties pēc 2012. gada Eiropas Kardiologu biedrības un Eiropas Sirds un Torakālo Ķirurgu asociācijas darba grupas sirds vārstuļu slimību ārstēšanas vadlīnijām. Pētījumā pirmoreiz Latvijas populācijā tika analizēti iekaisuma un neiekaisuma faktori, šūnu producētās regulējošās molekulas (citokīni) asins serumā un plazmā. Iegūtie rezultāti tika salīdzināti starp kontroles grupu un visām trijām AVS pakāpēm. Zinot jaunākos pētījumus par kalcificējošas AVS etiopatoģenēzi, tika noteikti iekaisuma un neiekaisuma faktori (hemerīns, FGF-21, TrxR1, MPO), kas līdz šim nav pētīti AVS pacientiem. Iegūtie rezultāti sniedz pilnīgāku informāciju par AVS patoģenēzi un analizēto iekaisuma un neiekaisuma faktoru savstarpējo saistību. Saistība starp hemerīnu un TrxR1 parāda, ka jau vieglā AVS pakāpē ir gan iekaisums, gan oksidatīvais stress. Pētījumā iegūtie dati ļauj spriest, ka hemerīns AVS pacientiem ir iekaisumu veicinošs. Hemerīns var tikt izmantots par vieglas aortas vārstuļa stenozes labu diagnostisko marķieri. Turpmāk būtu jāveido AV sklerozes pacientu novērošanas programma un jānosaka dinamikā hemerīns, lai noteiktu, vai ar šo biomarķieri iespējams prognozēt AVS attīstību. Analizējot FGF-21 līmeni AVS smaguma pakāpēs un tā saistību ar citiem faktoriem, var secināt, ka AVS attīstības sākumā tam ir pretiekaisuma darbība. Tālākajās AVS pakāpēs nevar viennozīmīgi noteikt FGF-21 lomu, jo tā var būt saistīta gan ar progresējošu kalcifikācijas procesu, gan pretdarbību miokarda hipertrofijai. Analizējot MMP un TIMP, mēs ieguvām tādus MMP-1 rezultātu, kas vedina domāt par ģenētiskā polimorfisma nozīmi AVS progresēšanas procesā. Turpmāk būtu lietderīgi pētīt MMP-1 polimorfismu, lai precizētu, vai 1G alēles nesējiem ir lēnāka AVS progresēšana. MPO līmeņa analīze un saistība ar ABL-H parāda, ka ABL-H ir netieši saistīts ar AVS procesu, jo oksidatīvā stresa apstākļos pieaug ox-ZBL-H līmenis, radot ABL-H disfunkciju un ox-ABL-H veidošanos. MPO un TrxR1 rezultāti liek domāt, ka vidēji smagā un smagā AVS pakāpē prevalē oksidatīvais stress un progresējoša kalcifikācija. Veiktais pētījums parāda, ka AVS ir aktīvs process visās smaguma pakāpēs, ko regulē iekaisums, oksidatīvais stress un no tiem atkarīga ekstracelulārās telpas remodelācija un progresējoša kalcifikācija. Pētījuma rezultāti liek pievērst īpašu uzmanību AV sklerozes un vieglas pakāpes AVS pacientiem, veikt to dinamisku novērošanu (ehokardiogrāfija, analīzes), lai atrastu citus biomarķierus, kas varētu prognozēt slimības progresēšanu.Item Iekaisīgie un neiekaisīgie riska faktori iegūtas aortas vārstuļa stenozes gadījumā. Promocijas darbs(Rīgas Stradiņa universitāte, 2019) Hofmanis, Juris; Mackēvičs, Vitolds; Tretjakovs, PēterisKalcificējoša aortas vārstuļa stenoze (AVS) izpaužas ar aortas vārstuļa (AV) viru fibro-kalcinējošu remodelāciju (pārveidošanos), kas ir lēni noritošs hroniska iekaisuma un kalcifikācijas process ar pilnībā neizzinātu un neviennozīmīgu etioloģiju un patoģenēzi. Pašlaik nav medikamentozas ārstēšanas, lai apturētu vai aizkavētu slimības progresēšanu. Vienīgā pieejamā ārstēšana ir ķirurģiska un AV nomaiņa vai transkatetrāla aortas vārstuļa implantācija. Pieaugot cilvēku dzīvildzei, pieaug to pacientu skaits, kuriem ir klīniski nozīmīga AVS. Gandrīz 25% cilvēku pēc 65 gadu vecuma ehokardiogrāfiski atrod AV sklerozi un apmēram 17% no šiem cilvēkiem turpmāk attīstās AVS. Laiks no AV sklerozes diagnosticēšanas līdz smagas AVS attīstībai vidēji ir 6–8 gadi. Pētnieciskā darba mērķis ir analizēt un noskaidrot, kuri no iekaisuma un kalcifikācijas procesā iesaistītajiem faktoriem, šūnu producētajām regulējošajām molekulām (citokīniem) un cik lielā mērā ietekmē AVS attīstību visās trīs AVS smaguma pakāpēs. Rezultātā varētu izdalīt kādu biomarķieri, ar kura palīdzību būtu iespējams prognozēt AVS progresēšanas ātrumu. Šūnu producētās regulējošās molekulas (citokīni) tika noteikti asins serumā un plazmā (tioredoksīna reduktāze-1, mieloperoksidāze). Pētnieciskā darba gaitā tika analizēta oksidatīvā stresa un iekaisuma mijiedarbība visās trijās AVS pakāpēs. Tāpat vēlreiz tika izvērtēta kopējā holesterīna un tā frakciju tieša un netieša ietekme uz AVS attīstību. Veiktais klīniski–analītiskais pētījums ir jaukta tipa prospektīvs gadījuma – kontroles pētījums. Brīvprātīgi tika atlasīti 102 pacienti, vadoties pēc iekļaušanas uz izslēgšanas kritērijiem un iedalīti divās pamatgrupās: kontroles grupā un AV stenozes grupā. Indivīdi kontroles grupā tika iekļauti atbilstoši ehokardiogrāfiski apstiprinātam veselam aortas vārstulim vecumā no 50 līdz 80 gadiem, kas atbilst AV stenozes pacientu vecumam, vadoties pēc 2012. gada Eiropas Kardiologu biedrības un Eiropas Sirds un Torakālo Ķirurgu asociācijas darba grupas sirds vārstuļu slimību ārstēšanas vadlīnijām. AV stenozes grupas pacienti tika sadalīti trīs apakšgrupās, atbilstoši AV stenozes pakāpei, vadoties pēc 2012. gada Eiropas Kardiologu biedrības un Eiropas Sirds un Torakālo Ķirurgu asociācijas darba grupas sirds vārstuļu slimību ārstēšanas vadlīnijām. Pētījumā pirmoreiz Latvijas populācijā tika analizēti iekaisuma un neiekaisuma faktori, šūnu producētās regulējošās molekulas (citokīni) asins serumā un plazmā. Iegūtie rezultāti tika salīdzināti starp kontroles grupu un visām trijām AVS pakāpēm. Zinot jaunākos pētījumus par kalcificējošas AVS etiopatoģenēzi, tika noteikti iekaisuma un neiekaisuma faktori (hemerīns, FGF-21, TrxR1, MPO), kas līdz šim nav pētīti AVS pacientiem. Iegūtie rezultāti sniedz pilnīgāku informāciju par AVS patoģenēzi un analizēto iekaisuma un neiekaisuma faktoru savstarpējo saistību. Saistība starp hemerīnu un TrxR1 parāda, ka jau vieglā AVS pakāpē ir gan iekaisums, gan oksidatīvais stress. Pētījumā iegūtie dati ļauj spriest, ka hemerīns AVS pacientiem ir iekaisumu veicinošs. Hemerīns var tikt izmantots par vieglas aortas vārstuļa stenozes labu diagnostisko marķieri. Turpmāk būtu jāveido AV sklerozes pacientu novērošanas programma un jānosaka dinamikā hemerīns, lai noteiktu, vai ar šo biomarķieri iespējams prognozēt AVS attīstību. Analizējot FGF-21 līmeni AVS smaguma pakāpēs un tā saistību ar citiem faktoriem, var secināt, ka AVS attīstības sākumā tam ir pretiekaisuma darbība. Tālākajās AVS pakāpēs nevar viennozīmīgi noteikt FGF-21 lomu, jo tā var būt saistīta gan ar progresējošu kalcifikācijas procesu, gan pretdarbību miokarda hipertrofijai. Analizējot MMP un TIMP, mēs ieguvām tādus MMP-1 rezultātu, kas vedina domāt par ģenētiskā polimorfisma nozīmi AVS progresēšanas procesā. Turpmāk būtu lietderīgi pētīt MMP-1 polimorfismu, lai precizētu, vai 1G alēles nesējiem ir lēnāka AVS progresēšana. MPO līmeņa analīze un saistība ar ABL-H parāda, ka ABL-H ir netieši saistīts ar AVS procesu, jo oksidatīvā stresa apstākļos pieaug ox-ZBL-H līmenis, radot ABL-H disfunkciju un ox-ABL-H veidošanos. MPO un TrxR1 rezultāti liek domāt, ka vidēji smagā un smagā AVS pakāpē prevalē oksidatīvais stress un progresējoša kalcifikācija. Veiktais pētījums parāda, ka AVS ir aktīvs process visās smaguma pakāpēs, ko regulē iekaisums, oksidatīvais stress un no tiem atkarīga ekstracelulārās telpas remodelācija un progresējoša kalcifikācija. Pētījuma rezultāti liek pievērst īpašu uzmanību AV sklerozes un vieglas pakāpes AVS pacientiem, veikt to dinamisku novērošanu (ehokardiogrāfija, analīzes), lai atrastu citus biomarķierus, kas varētu prognozēt slimības progresēšanu.Item Inflammatory and Non-Inflammatory Risk Factors in Acquired Aortic Valve Stenosis. Doctoral Thesis(Rīga Stradiņš University, 2019) Hofmanis, Juris; Mackēvičs, Vitolds; Tretjakovs, PēterisCalcific stenosis of the aortic valve (AVS) manifests with fibro-calcific remodelation (transformation) of the aortic valve (AV), which is a slow process of chronic inflammation and calcification with completely unexplored and ambiguous etiology and pathogenesis. Currently, there is no medical treatment to stop or delay the progression of the disease. The only treatment available is a surgical replacement of AV or transcathether aortic valve implantation. With increasing people’s survival the number of patients with clinically relevant AVS is increasing. Almost in 25% of people after the age of 65 echocardiographically AV sclerosis is found and about 17% of these people further develop AVS. The time between diagnosis of AV sclerosis and development of severe AVS is on average 6–8 years. The aim of the research work is to analyze and find out which factors involved in the inflammation and calcification process, cell-produced regulatory molecules (cytokines) affect AVS development in all three AVS severity degrees and to what extent. As a result, some biomarkers could be isolated to predict the rate of progression of AVS. Cell-produced regulatory molecules (cytokines) were detected in blood serum and plasma (thioredoxin reductase-1, mieloperoxidase). The interaction of oxidative stress and inflammation in all three AVS severity degrees was analyzed during the research work. The direct and indirect effects of total cholesterol and its fractions on the development of AVS were also re-evaluated. The conducted clinical-analytical study is a prospective case-control study of mixed type. 102 patients were selected voluntarily according to inclusion and exclusion criteria and divided into two basic groups: the control group and the AVS group. Individuals in the control group were included according to an echocardiographically approved healthy aortic valve between the age of 50 to 80 years, which corresponds to the AVS patients' age at the 2012 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery Guidelines for the management of valvular heart disease. Patients of the AVS group were divided into three subgroups according to the degree of the AV stenosis, based on the 2012 European Society of Cardiology and the European Association for Cardio–Thoracic Surgery Guidelines for the Management of Valvular Heart Disease. In the study for the first time in the Latvia population, inflammatory and noninflammatory factors, cell-produced regulatory molecules (cytokines) in blood serum and plasma were analyzed. The obtained results were compared between the control group and all three AVS grades. Knowing recent studies on etiopathogenesis of the calcific AVS, inflammatory and noninflammatory factors (chemerin, FGF-21, TrxR1 and MPO) that have not been studied in AVS patients so far were identified. The obtained results provide more complete information on the pathogenesis of AVS and the correlation between the analyzed inflammatory and non-inflammatory factors. The relationship between chemerin and TrxR1 shows that inflammation and oxidative stress are already present in the mild AVS grade. The results obtained in the study allow to suggest that chemerin in AVS patients promotes inflammation. Chemerin can be used AVS a good diagnostic marker for the mild AVS. Hereafter, a follow-up program for the AV sclerosis patients should be developed and chemerin should be determined in dynamics to find out whether this biomarker can predict the development of AVS. Analyzing level of FGF-21 in AVS severity grades and its correlation with other factors, it can be concluded that it has anti-inflammatory activity at the beginning of AVS development. FGF-21 role in the subsequent AVS severity grades cannot be unequivocally define AVS it may be associated with both progressive calcification process and counteraction to myocardial hypertrophy. When analyzing MMP and TIMP, we obtained the result of MMP-1 that suggests the role of genetic polymorphism in the progression process of AVS. In the future, it would be useful to study MMP-1 polymorphism to clarify whether 1G allele carriers have slower AVS progression. Analysis of the MPO level and its association with HDL-C shows that HDL-C is indirectly associated with the AVS process, AVS ox-LDL-C levels increase under oxidative stress conditions, resulting in HDL-C dysfunction and formation of ox-HDL-C. The results of MPO and TrxR1 suggest that oxidative stress and progressive calcification are prevalent in moderate to severe AVS. The conducted study shows that AVS is an active process in all degrees of severity regulated by inflammation, oxidative stress, and extracellular remodeling and progressive calcification which depends on them. The results of the study suggest that special attention should be paid to the patients with AV sclerosis and mild AVS, their dynamic monitoring (echocardiography, analysis) should be done to find other biomarkers that can predict disease progression.Item Inflammatory and Non-Inflammatory Risk Factors in Acquired Aortic Valve Stenosis. Summary of the Doctoral Thesis(Rīga Stradiņš University, 2019) Hofmanis, Juris; Mackēvičs, Vitolds; Tretjakovs, PēterisCalcific stenosis of the aortic valve (AVS) manifests with fibro-calcific remodelation (transformation) of the aortic valve (AV), which is a slow process of chronic inflammation and calcification with completely unexplored and ambiguous etiology and pathogenesis. Currently, there is no medical treatment to stop or delay the progression of the disease. The only treatment available is a surgical replacement of AV or transcathether aortic valve implantation. With increasing people’s survival the number of patients with clinically relevant AVS is increasing. Almost in 25% of people after the age of 65 echocardiographically AV sclerosis is found and about 17% of these people further develop AVS. The time between diagnosis of AV sclerosis and development of severe AVS is on average 6–8 years. The aim of the research work is to analyze and find out which factors involved in the inflammation and calcification process, cell-produced regulatory molecules (cytokines) affect AVS development in all three AVS severity degrees and to what extent. As a result, some biomarkers could be isolated to predict the rate of progression of AVS. Cell-produced regulatory molecules (cytokines) were detected in blood serum and plasma (thioredoxin reductase-1, mieloperoxidase). The interaction of oxidative stress and inflammation in all three AVS severity degrees was analyzed during the research work. The direct and indirect effects of total cholesterol and its fractions on the development of AVS were also re-evaluated. The conducted clinical-analytical study is a prospective case-control study of mixed type. 102 patients were selected voluntarily according to inclusion and exclusion criteria and divided into two basic groups: the control group and the AVS group. Individuals in the control group were included according to an echocardiographically approved healthy aortic valve between the age of 50 to 80 years, which corresponds to the AVS patients' age at the 2012 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery Guidelines for the management of valvular heart disease. Patients of the AVS group were divided into three subgroups according to the degree of the AV stenosis, based on the 2012 European Society of Cardiology and the European Association for Cardio–Thoracic Surgery Guidelines for the Management of Valvular Heart Disease. In the study for the first time in the Latvia population, inflammatory and noninflammatory factors, cell-produced regulatory molecules (cytokines) in blood serum and plasma were analyzed. The obtained results were compared between the control group and all three AVS grades. Knowing recent studies on etiopathogenesis of the calcific AVS, inflammatory and noninflammatory factors (chemerin, FGF-21, TrxR1 and MPO) that have not been studied in AVS patients so far were identified. The obtained results provide more complete information on the pathogenesis of AVS and the correlation between the analyzed inflammatory and non-inflammatory factors. The relationship between chemerin and TrxR1 shows that inflammation and oxidative stress are already present in the mild AVS grade. The results obtained in the study allow to suggest that chemerin in AVS patients promotes inflammation. Chemerin can be used AVS a good diagnostic marker for the mild AVS. Hereafter, a follow-up program for the AV sclerosis patients should be developed and chemerin should be determined in dynamics to find out whether this biomarker can predict the development of AVS. Analyzing level of FGF-21 in AVS severity grades and its correlation with other factors, it can be concluded that it has anti-inflammatory activity at the beginning of AVS development. FGF-21 role in the subsequent AVS severity grades cannot be unequivocally define AVS it may be associated with both progressive calcification process and counteraction to myocardial hypertrophy. When analyzing MMP and TIMP, we obtained the result of MMP-1 that suggests the role of genetic polymorphism in the progression process of AVS. In the future, it would be useful to study MMP-1 polymorphism to clarify whether 1G allele carriers have slower AVS progression. Analysis of the MPO level and its association with HDL-C shows that HDL-C is indirectly associated with the AVS process, AVS ox-LDL-C levels increase under oxidative stress conditions, resulting in HDL-C dysfunction and formation of ox-HDL-C. The results of MPO and TrxR1 suggest that oxidative stress and progressive calcification are prevalent in moderate to severe AVS. The conducted study shows that AVS is an active process in all degrees of severity regulated by inflammation, oxidative stress, and extracellular remodeling and progressive calcification which depends on them. The results of the study suggest that special attention should be paid to the patients with AV sclerosis and mild AVS, their dynamic monitoring (echocardiography, analysis) should be done to find other biomarkers that can predict disease progression.Item Prognostic utility of circulating growth factors in aortic valve stenosis : A pilot study(2021-01) Hofmanis, Juris; Tretjakovs, Peteris; Svirskis, Simons; Gersone, Gita; Hofmane, Dace; Rozenberga, Ulla; Blumfelds, Leons; Bahs, Guntis; Lejnieks, Aivars; Mackevics, Vitolds; Faculty of MedicineBackground and Objectives: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree (p < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker (p < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.Item Prognostic utility of circulating growth factors in aortic valve stenosis : A pilot study(2021-01) Hofmanis, Juris; Tretjakovs, Peteris; Svirskis, Simons; Gersone, Gita; Hofmane, Dace; Rozenberga, Ulla; Blumfelds, Leons; Bahs, Guntis; Lejnieks, Aivars; Mackevics, Vitolds; Faculty of MedicineBackground and Objectives: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree (p < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker (p < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.Item Prognostic utility of novel biomarkers in aortic valve stenosis(2019-05-01) Tretjakovs, Peteris; Hofmanis, Juris; Hofmane, Dace; Krieviņa, Gita; Blumfelds, Leons; Mackevičs, Vitolds; Lejnieks, Aivars; Bahs, Guntis; Faculty of MedicineThe aim of the present study was to evaluate plasma levels of chemerin, myeloperoxidase (MPO), fibroblast growth factor-21 (FGF-21), thioredoxin reductase-1 (TrxR1), and matrix metallopeptidase-9 (MMP-9) in acquired aortic valve (AoV) stenosis patients to determine correlations between the studied cellular factors, and also clarify the predictive values of these factors as biomarkers in AoV stenosis. AoV stenosis patients were classified into three groups: 17 patients with mild AoV stenosis; 19 with moderate and 15 with severe AoV stenosis. Twenty-four subjects without AoV stenosis were selected as a control group. Our findings suggest that AoV stenosis might be associated with increased chemerin, TrxR1, MPO, and FGF-21 levels in plasma. Moreover, these factors and also MMP-9 already reached statistically significantly elevated levels in the early stages of AoV stenosis, but MPO levels were more pronounced in patients with moderate and severe AoV stenosis. Chemerin was correlated with all of the studied cytokines; TrxR1 and MMP-9 were correlated with several other cellular factors. Our findings (by ROC analysis) suggest that MPO and chemerin might serve as specific and sensitive biomarkers for AoV stenosis without grading the severity, but, in relation to mild AoV stenosis, TrxR1, FGF-21, and MMP-9 also reached good or moderate levels as biomarkers. The cellular factors might serve as novel diagnostic and prognostic biomarkers in AoV stenosis patients, while chemerin and MPO may be more powerful.