Short-Term Disruption of Diurnal Rhythms After Murine Myocardial Infarction Adversely Affects Long-Term Myocardial Structure and Function

Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca2+-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated ( n = 6) and untreated ( n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 ± 2% pre-MI to 30 ± 4% with MI only vs. 41 ± 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 ± 2 μl pre-MI to 73 ± 4 μl with MI only vs. 55 ± 4 μl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients.

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The Effect of Perfluorooctane Sulfonate, Exposure Time, and Chemical Mixtures on Methanogenic Community Structure and Function

Microbiology Insights ◽

10.4137/mbi.s31345 ◽

2015 ◽

Vol 8s2 ◽

pp. MBI.S31345 ◽

Cited By ~ 1

Author(s):

Patrick J. McNamara ◽

Timothy M. LaPara ◽

Paige J. Novak

Keyword(s):

Community Structure ◽

Exposure Time ◽

Methane Production ◽

Perfluorooctane Sulfonate ◽

Structure And Function ◽

Short Term ◽

Anaerobic Digesters ◽

And Function ◽

The Impact

A plethora of organic micropollutant mixtures are found in untreated municipal wastewater. Anaerobic digesters receive large loadings of hydrophobic micropollutants that sorb to wastewater biosolids. Despite micropollutants being pervasive as mixtures, little research is available to explain the impact that mixtures of compounds, as well as exposure time, have on microbial communities in anaerobic digesters. Perfluorooctane sulfonate (PFOS) was added to anaerobic enrichment cultures in both short-term (14 days) and long-term (140 days) studies to determine the impact of exposure time. Additionally, triclosan was added during the experiments to investigate the impact of mixtures on community structure and function. PFOS did not alter methane production in short-term studies, but in long-term studies, methane production increased, consistent with our hypothesis that PFOS may act as a metabolic uncoupler. The impact of triclosan on methane production was exacerbated when PFOS was already present in the anaerobic enrichment cultures. Triclosan also had greater impacts on microbial community structures in the bottles that had been exposed to PFOS long-term. These results demonstrate that both chemical mixtures and exposure time are important parameters to address when trying to define the impacts of micropollutants on anaerobic microbial communities.

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Changes in Liver Structure and Function after Short-Term and Long-Term Treatment of Rats with Dehydroepiandrosterone

Journal of Nutrition ◽

10.1093/jn/122.4.967 ◽

1992 ◽

Vol 122 (4) ◽

pp. 967-976 ◽

Cited By ~ 31

Author(s):

Monica Bellei ◽

Daniela Battelli ◽

Claudio Fornieri ◽

Giuseppe Mori ◽

Umberto Muscatello ◽

...

Keyword(s):

Term Treatment ◽

Structure And Function ◽

Short Term ◽

Long Term Treatment ◽

Liver Structure ◽

And Function

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Plasma MMP-2, MMP-9 and N-BNP in Long-Term Survivors Following Complicated Myocardial Infarction: Relation to Cardiac Magnetic Resonance Imaging Measures of Left Ventricular Structure and Function

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2007.07.006 ◽

2007 ◽

Vol 13 (10) ◽

pp. 843-849 ◽

Cited By ~ 26

Author(s):

Stein Orn ◽

Cord Manhenke ◽

Iain B. Squire ◽

Leong Ng ◽

Inder Anand ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Myocardial Infarction ◽

Cardiac Magnetic Resonance ◽

Left Ventricular ◽

Structure And Function ◽

Resonance Imaging ◽

Ventricular Structure ◽

And Function ◽

Long Term Survivors

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Abstract 262: Knockout of Type VI Collagen Preserves Mitochondrial Structure and Function Following Myocardial Infarction

Circulation Research ◽

10.1161/res.117.suppl_1.262 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

J G Meszaros ◽

Daniel J Luther ◽

Patrick T Kang ◽

Yeong-Renn Chen ◽

R Lance Miller ◽

...

Keyword(s):

Myocardial Infarction ◽

Respiratory Control ◽

Ischemic Injury ◽

Structure And Function ◽

Matrix Proteins ◽

Mitochondrial Morphology ◽

Mitochondrial Structure ◽

Transmission Electron ◽

And Function

Cardiac remodeling is a dynamic process that is accelerated after myocardial infarction (MI), and the traditional focus of key extracellular matrix proteins that mediate remodeling has been on the fibrillar types I and III collagen. We have previously reported that knockout mice of the lesser-known, non-fibrillar collagen VI (Col6-/-) are protected from MI injury as evidenced by significantly reduced infarct size, fibrosis and apoptosis leading to preserved long-term cardiac function. Determining the mechanisms underlying this cardioprotection is the goal of this study. Interestingly, the Col6-/- mice are a model for Bethlam Myopathy, a rare skeletal muscular dystrophy that is characterized by mitochondrial dysfunction leading to premature apoptosis of skeletal myocytes. We hypothesized that alterations in mitochondrial structure and function in the myocardium of Col6-/- mice may play key mechanistic roles responses to ischemic injury. Mitochondrial morphology was visualized by transmission electron microscopy to compare pre- and post-MI changes. Mitochondria from uninjured Col6-/- LV tissue had similar morphology as WT, and at 3 days post-MI the mitochondrial morphology was similarly compromised in both WT and Col6-/- mice. However, at 14 days post-MI the Col6-/- mitochondria were less swollen (43 ± 5.1% decrease in overall volume) and displayed improved orientation/organization over WT (continuous strands). We measured basal O2 consumption and 24 hours post-MI in mitochondria isolated from the infarcted zones of both genotypes. The respiratory control index (RCI) of the Col6-/- mitochondria was lower in the basal, uninjured hearts (7.2 ± 0.9 in WT vs. 4.9 ± 0.6 in Col6-/-). However, the RCI of mitochondria in the infarcted region of Col6-/- hearts at 24 hours post-MI declined less than WT (post-MI values of 2.7 ± 0.5 in WT vs. 2.8 ± 0.7 in Col6-/-) . These data indicate that Col6-/- mice have preserved mitochondrial morphology and a smaller decline in respiration following MI, which may represent a novel homeostatic mechanism underlying protection from ischemic injury in the Col6-/- heart.

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Cardiac structure and function in lowlanders at high altitude: short-term adaptation and chronic remodeling

10.22541/au.161932783.35381962/v1 ◽

2021 ◽

Author(s):

guyue liu ◽

liming zhao ◽

qing xu ◽

rong xiao ◽

mingjian lang

Keyword(s):

Sea Level ◽

Structure And Function ◽

Cardiac Structure ◽

Short Term ◽

Right Heart ◽

Short Term Exposure ◽

Short Term Adaptation ◽

Cardiac Structure And Function ◽

And Function

Aims: The purpose of this study was to examine cardiac structure and function in lowlanders at high altitude(HA) to investigate short-term adaptation and long-term cardiac remodeling. Methods: In total of 301 healthy subjects included in this study, short-term exposed (STE) and acclimatized lowlanders (AL) at HA, native Tibetans(NT) and sea level residents(SLR) were comprised of 75,77,69 and 80 participants, respectively. Standard echocardiography was performed on all groups, subjects at HA were examined after return to sea level in <24 hours. Results: SBP and HR did not increase significantly after short-term exposure to HA in STE, but increased after long-term exposure in AL, which could be detected even after returning to the plain. Exposure to HA enlarged right heart, widened pulmonary artery and reduced left ventricular(LV) diastolic function in lowlanders. The degree of diastolic dysfunction was more obvious in AL. LV wall thickness increased even after short-term exposure to HA in lowlanders. Ejection fraction did not change significantly in STE, but decreased in AL. Conclusions: Exposure to HA could enlarged the right heart and decrease the diastolic function of LV in lowlanders. The LV systolic function was preserved after short-term HA exposure, but decreased after long-term HA exposure.

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