Background-Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure. Methods and Results-Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV internal dimension in diastole was increased in PTU-S and PTU-L rats, but only PTU-L rats showed a significant increase in myocyte length due to series sarcomere addition.Resting and maximum (adenosine) myocardial blood flow were reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large reduction in arteriolar length density and small arterioles in PTU-S and PTU-L (PϽ0.05 or greater for all of the above comparisons). Expression of sarcoplasmic/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA)-2a and ␣-myosin heavy chain were reduced in hypothyroidism, whereas phospholamban and -myosin heavy chain were increased. Conclusions-Hypothyroidism led to severe, progressive systolic dysfunction and increased chamber diameter/wall thickness ratio despite a reduction in cardiac mass. Chamber dilatation in PTU-L rats was due to series sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired myocardial blood flow due to a dramatic loss of arterioles. Thus, we have identified 2 important new mechanisms by which low thyroid function may lead to heart failure. (Circulation. 2005;112:3122-3130.)
Nanomaterials
that combine multimodality imaging and therapeutic
functions within a single nanoplatform have drawn extensive attention
for molecular medicines and biological applications. Herein, we report
a theranostic nanoplatform based on a relatively smaller (<20 nm)
iron oxide loaded porphyrin-grafted lipid nanoparticles (Fe3O4@PGL NPs). The amphiphilic PGL easily self-assembled
on the hydrophobic exterior surface of ultrasmall Fe3O4 NPs, resulting in a final ultrasmall Fe3O4@PGL NPs with diameter of ∼10 nm. The excellent self-assembling
nature of the as-synthesized PGL NPs facilitated a higher loading
of porphyrins, showed a negligible dark toxicity, and demonstrated
an excellent photodynamic effect against HT-29 cancer cells in vitro. The in vivo experimental results
further confirmed that Fe3O4@PGL NPs were ideally
qualified for both the fluorescence and magnetic resonance (MR) imaging
guided nanoplatforms to track the biodistribution and therapeutic
responses of NPs as well as to simultaneously trigger the generation
of highly cytotoxic reactive oxygen species (ROS) necessary for excellent
photodynamic therapy (PDT). After recording convincing therapeutic
responses, we further evaluated the ability of Fe3O4@PGL NPs/Fe3O4@Lipid NPs for ferroptosis
therapy (FT) via tumor microenvironment (TME) modulation for improved
anticancer activity. We hypothesized that tumor-associated macrophages
(TAMs) could significantly improve the efficacy of FT by accelerating
the Fenton reaction in vitro. In our results, the
Fe ions released in vitro directly contributed to
the Fenton reaction, whereas the presence of RAW 264.7 macrophages
further accelerated the ROS generation as observed by the fluorescence
imaging. The significant increase in the ROS during the coincubation
of NPs, endocytosed by HT-29 cells and RAW264.7 cells, further induced
increased cellular toxicity of cancer cells.
USP18 associates with and deubiquitinates TAK1 to protect against hepatic steatosis, insulin resistance, and the inflammatory response. (Hepatology 2017;66:1866-1884).
Hepatocyte DUSP14 is required for maintaining hepatic metabolic homeostasis and for suppressing inflammation, a novel function that relies on constraining TAK1 hyperactivation. (Hepatology 2018;67:1320-1338).
We found a clear association between thyroid dysfunction and increased risk of mortality in idiopathic dilated cardiomyopathy with HF. These results suggest that monitoring thyroid function in HF patients is necessary, and further studies on the treatment of HF with thyroid dysfunction are needed.
Interventional FL management, using the FLIRT concept, is feasible in selected cases of aortic dissection, promotes FL thrombosis and induces successful remodelling.
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