@article{TraubGrondeyGassenmaieretal.2022,
  author    = {Traub, Jan and Grondey, Katja and Gassenmaier, Tobias and Schmitt, Dominik and Fette, Georg and Frantz, Stefan and Boivin-Jahns, Val{\´e}rie and Jahns, Roland and St{\"o}rk, Stefan and Stoll, Guido and Reiter, Theresa and Hofmann, Ulrich and Weber, Martin S. and Frey, Anna},
  title     = {Sustained increase in serum glial fibrillary acidic protein after first ST-elevation myocardial infarction},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  issn      = {1422-0067},
  doi       = {10.3390/ijms231810304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288261},
  year      = {2022},
  abstract  = {Acute ischemic cardiac injury predisposes one to cognitive impairment, dementia, and depression. Pathophysiologically, recent positron emission tomography data suggest astroglial activation after experimental myocardial infarction (MI). We analyzed peripheral surrogate markers of glial (and neuronal) damage serially within 12 months after the first ST-elevation MI (STEMI). Serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using ultra-sensitive molecular immunoassays. Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11\% female). The median (quartiles) of GFAP was 63.8 (47.0, 89.9) pg/mL and of NfL 10.6 (7.2, 14.8) pg/mL at study entry 0-4 days after STEMI. GFAP after STEMI increased in the first 3 months, with a median change of +7.8 (0.4, 19.4) pg/mL (p = 0.007). It remained elevated without further relevant increases after 6 months (+11.7 (0.6, 23.5) pg/mL; p = 0.015), and 12 months (+10.3 (1.5, 22.7) pg/mL; p = 0.010) compared to the baseline. Larger relative infarction size was associated with a higher increase in GFAP (ρ = 0.41; p = 0.009). In contrast, NfL remained unaltered in the course of one year. Our findings support the idea of central nervous system involvement after MI, with GFAP as a potential peripheral biomarker of chronic glial damage as one pathophysiologic pathway.},
  language  = {en}
}
@article{ChenLiuWeidemannetal.2021,
  author    = {Chen, Menjia and Liu, Dan and Weidemann, Frank and Lengenfelder, Bj{\"o}rn Daniel and Ertl, Georg and Hu, Kai and Frantz, Stefan and Nordbeck, Peter},
  title     = {Echocardiographic risk factors of left ventricular thrombus in patients with acute anterior myocardial infarction},
  series = {ESC Heart Failure},
  volume    = {8},
  journal   = {ESC Heart Failure},
  number    = {6},
  doi       = {10.1002/ehf2.13605},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261067},
  pages     = {5248-5258},
  year      = {2021},
  abstract  = {Aims This study aimed to identify echocardiographic determinants of left ventricular thrombus (LVT) formation after acute anterior myocardial infarction (MI). Methods and results This case-control study comprised 55 acute anterior MI patients with LVT as cases and 55 acute anterior MI patients without LVT as controls, who were selected from a cohort of consecutive patients with ischemic heart failure in our hospital. The cases and controls were matched for age, sex, and left ventricular ejection fraction. LVT was detected by routine/contrast echocardiography or cardiac magnetic resonance imaging during the first 3 months following MI. Formation of apical aneurysm after MI was independently associated with LVT formation [72.0\% vs. 43.5\%, odds ratio (OR) = 5.06, 95\% confidence interval (CI) 1.65-15.48, P = 0.005]. Echocardiographic risk factors associated with LVT formation included reduced mitral annular plane systolic excursion (<7 mm, OR = 4.69, 95\% CI 1.84-11.95, P = 0.001), moderate-severe diastolic dysfunction (OR = 2.71, 95\% CI 1.11-6.57, P = 0.028), and right ventricular (RV) dysfunction [reduced tricuspid annular plane systolic excursion < 17 mm (OR = 5.48, 95\% CI 2.12-14.13, P < 0.001), reduced RV fractional area change < 0.35 (OR = 3.32, 95\% CI 1.20-9.18, P = 0.021), and enlarged RV mid diameter (per 5 mm increase OR = 1.62, 95\% CI 1.12-2.34, P = 0.010)]. Reduced tricuspid annular plane systolic excursion (<17 mm) significantly associated with increased risk of LVT in anterior MI patients (OR = 3.84, 95\% CI 1.37-10.75, P = 0.010), especially in those patients without apical aneurysm (OR = 5.12, 95\% CI 1.45-18.08, P = 0.011), independent of body mass index, hypertension, anaemia, mitral annular plane systolic excursion, and moderate-severe diastolic dysfunction. Conclusions Right ventricular dysfunction as determined by reduced TAPSE or RV fractional area change is independently associated with LVT formation in acute anterior MI patients, especially in the setting of MI patients without the formation of an apical aneurysm. This study suggests that besides assessment of left ventricular abnormalities, assessment of concomitant RV dysfunction is of importance on risk stratification of LVT formation in patients with acute anterior MI.},
  language  = {en}
}
@article{PoppSchmittBoehrerLangeretal.2021,
  author    = {Popp, Sandy and Schmitt-B{\"o}hrer, Angelika and Langer, Simon and Hofmann, Ulrich and Hommers, Leif and Schuh, Kai and Frantz, Stefan and Lesch, Klaus-Peter and Frey, Anna},
  title     = {5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {14},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10143104},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242739},
  year      = {2021},
  abstract  = {Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally na{\"i}ve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (-/-) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT-/- mice with infarct sizes >30\% experienced 100\% mortality, while 50\% of 5-HTT+/- and 37\% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30\%) 5-HTT-/- mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT-/- mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.},
  language  = {en}
}
@article{PachelMathesBayeretal.2013,
  author    = {Pachel, Christina and Mathes, Denise and Bayer, Barbara and Dienesch, Charlotte and Wangorsch, Gaby and Heitzmann, Wolfram and Lang, Isabell and Ardehali, Hossein and Ertl, Georg and Dandekar, Thomas and Wajant, Harald and Frantz, Stefan},
  title     = {Exogenous Administration of a Recombinant Variant of TWEAK Impairs Healing after Myocardial Infarction by Aggravation of Inflammation},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0078938},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129889},
  pages     = {e78938},
  year      = {2013},
  abstract  = {Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factorinducible 14 (Fn14) are upregulated after myocardial infarction (MI) in both humans and mice. They modulate inflammation and the extracellular matrix, and could therefore be important for healing and remodeling after MI. However, the function of TWEAK after MI remains poorly defined. Methods and results: Following ligation of the left coronary artery, mice were injected twice per week with a recombinant human serum albumin conjugated variant of TWEAK (HSA-Flag-TWEAK), mimicking the activity of soluble TWEAK. Treatment with HSA-Flag-TWEAK resulted in significantly increased mortality in comparison to the placebo group due to myocardial rupture. Infarct size, extracellular matrix remodeling, and apoptosis rates were not different after MI. However, HSA-Flag-TWEAK treatment increased infiltration of proinflammatory cells into the myocardium. Accordingly, depletion of neutrophils prevented cardiac ruptures without modulating all-cause mortality. Conclusion: Treatment of mice with HSA-Flag-TWEAK induces myocardial healing defects after experimental MI. This is mediated by an exaggerated neutrophil infiltration into the myocardium.},
  language  = {en}
}
@article{FreyPoppPostetal.2014,
  author    = {Frey, Anna and Popp, Sandy and Post, Antonia and Langer, Simon and Lehmann, Marc and Hofmann, Ulrich and Siren, Anna-Leena and Hommers, Leif and Schmitt, Angelika and Strekalova, Tatyana and Ertl, Georg and Lesch, Klaus-Peter and Frantz, Stefan},
  title     = {Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain},
  series = {Frontiers in Behavioral Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Behavioral Neuroscience},
  issn      = {1662-5153},
  doi       = {10.3389/fnbeh.2014.00376},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118234},
  pages     = {376},
  year      = {2014},
  abstract  = {Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI). Methods and Results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.},
  language  = {en}
}