Kardioloogia

Eesti Arst 2016; 95(8):54

Kardioloogia

Eesti Arst 2011; 90(5):23

Rasedusaegne aordi dilatatsiooni ja bikuspiidse aordiklapi operatsioon Turneri sündroomiga patsiendil. Haigusjuhu kirjeldus

Rasedusaegne südameoperatsioon kätkeb endas suurt riski nii emale kui ka lootele. On kirjeldatud vaid üksikud aorditüve ja aordiklapi operatsioone raseduse ajal. Kirjanduse andmetel on loote suremus ekstrakorporaalse vereringe kasutamisel 20%. Operatsiooniaegne hüpotermia halvendab uteroplatsentaarset perfusiooni ja soodustab emaka kontraktsioonide teket. Hüperkaleemia emal võib põhjustada lootel bradükardiat ja düstressi. Artiklis on kirjeldatud raseduse kulgu Turneri sündroomiga 31-aastasel patsiendil, kellel aordianeurüsm diameetriga 5 cm ning bikuspiidne aordiklapp diagnoositi esimest korda raseduse ajal. Patsiendile tehti raseduse 13. nädalal Bentalli operatsioon (aordiklapi ja üleneva aordi proteesimine). Rasedus jätkus ning patsient sünnitas raseduse 36. nädalal keisrilõike teel poja sünnikaaluga 1950 g, Apgari hinded olid 8 ja 9 palli. 5 kuu vanusena kaalus laps 6,5 kg ja oli normaalse emotsionaalse arenguga. Ka naise tervis on hea.Eesti Arst 2015; 94(6):365–36

Hüperoksia – kas uus võimalus südamelihase kaitseks?

Aeroobsetele organismidele on hapnik elutähtis ja hapniku defitsiit viib organismi kahjustusele. Nii südamelihase isheemia reperfusioonikahjustuse kui ka isheemilise eelkohastumuse patofüsioloogias mängivad olulist osa hapniku reaktiivsed osakesed. Hapniku kõrge osarõhk ja kestev ekspositsioon võivad põhjustada hapniku reaktiivsete osakeste kestva liigproduktsiooni, mis ületab organismi antioksüdantse kaitsevõime ja kutsub esile kahjustava oksüdatiivse stressi. Samas on hapniku reaktiivsetel osakestel oluline füsioloogiline roll rakkude signaalmolekulidena, mis osalevad rakusiseste adaptatsioonimehhanismide aktivatsioonil. Eesti Arst 2003; 82 (1): 22–2

Humaniin – väike peptiid, suured ülesanded? Ülevaateartikkel humaniini-nimelisest peptiidist

Aastal 2001 kirjeldati esimest korda humaniini-nimelist peptiidi, mis võib olla esimene nn mitokondriaalne signaalmolekul. Praeguseks on kõnealusel peptiidil kirjeldatud mitmeid positiivseid omadusi: antiapoptootiline toime, tsütoprotektsioon mitmete mehhanismide kaudu. Peptiidi seostatakse vanusega seotud haigustega, näiteks diabeedi ja ateroskleroosiga. Artiklis on tutvustatud humaniini kui peptiidi, millest loodetakse potentsiaalset siirdemeditsiinilist läbimurret.Eesti Arst 2017; 96(6):328–33

Plasma cortisol-linked gene networks in hepatic and adipose tissues implicate corticosteroid-binding globulin in modulating tissue glucocorticoid action and cardiovascular risk

Genome-wide association meta-analysis (GWAMA) by the Cortisol Network (CORNET) consortium identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14 associated with morning plasma cortisol, cardiovascular disease (CVD), and SERPINA6 mRNA expression encoding corticosteroid-binding globulin (CBG) in the liver. These and other findings indicate that higher plasma cortisol levels are causally associated with CVD; however, the mechanisms by which variations in CBG lead to CVD are undetermined. Using genomic and transcriptomic data from The Stockholm Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) study, we identified plasma cortisol-linked single-nucleotide polymorphisms (SNPs) that are trans-associated with genes from seven different vascular and metabolic tissues, finding the highest representation of trans-genes in the liver, subcutaneous fat, and visceral abdominal fat, [false discovery rate (FDR) = 15%]. We identified a subset of cortisol-associated trans-genes that are putatively regulated by the glucocorticoid receptor (GR), the primary transcription factor activated by cortisol. Using causal inference, we identified GR-regulated trans-genes that are responsible for the regulation of tissue-specific gene networks. Cis-expression Quantitative Trait Loci (eQTLs) were used as genetic instruments for identification of pairwise causal relationships from which gene networks could be reconstructed. Gene networks were identified in the liver, subcutaneous fat, and visceral abdominal fat, including a high confidence gene network specific to subcutaneous adipose (FDR = 10%) under the regulation of the interferon regulatory transcription factor, IRF2. These data identify a plausible pathway through which variation in the liver CBG production perturbs cortisol-regulated gene networks in peripheral tissues and thereby promote CVD

Correction to: Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits

Erratum for Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits. [BMC Med Genomics. 2019

Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC’s systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.publishedVersio