Browsing by Subject "Aorta"

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Open Access
Jnk1 deficiency in hematopoietic cells suppresses macrophage apoptosis and increases atherosclerosis in low-density lipoprotein receptor null mice
(Lippincott Williams and Wilkins, 2016) Babaev, V. R.; Yeung, M.; Erbay, E.; Ding, L.; Zhang, Y.; May, J. M.; Fazio, S.; Hotamisligil, G. S.; Linton, M. F.
Objective - The c-Jun NH 2 -terminal kinases (JNK) are regulated by a wide variety of cellular stresses and have been implicated in apoptotic signaling. Macrophages express 2 JNK isoforms, JNK1 and JNK2, which may have different effects on cell survival and atherosclerosis. Approach and Results - To dissect the effect of macrophage JNK1 and JNK2 on early atherosclerosis, Ldlr-/- mice were reconstituted with wild-type, Jnk1-/-, and Jnk2-/- hematopoietic cells and fed a high cholesterol diet. Jnk1-/- →Ldlr-/- mice have larger atherosclerotic lesions with more macrophages and fewer apoptotic cells than mice transplanted with wild-type or Jnk2-/- cells. Moreover, genetic ablation of JNK to a single allele (Jnk1+/- /Jnk2-/- or Jnk1-/- /Jnk2+/-) in marrow of Ldlr-/- recipients further increased atherosclerosis compared with Jnk1-/- →Ldlr-/- and wild-type→Ldlr-/- mice. In mouse macrophages, anisomycin-mediated JNK signaling antagonized Akt activity, and loss of Jnk1 gene obliterated this effect. Similarly, pharmacological inhibition of JNK1, but not JNK2, markedly reduced the antagonizing effect of JNK on Akt activity. Prolonged JNK signaling in the setting of endoplasmic reticulum stress gradually extinguished Akt and Bad activity in wild-type cells with markedly less effects in Jnk1-/- macrophages, which were also more resistant to apoptosis. Consequently, anisomycin increased and JNK1 inhibitors suppressed endoplasmic reticulum stress-mediated apoptosis in macrophages. We also found that genetic and pharmacological inhibition of phosphatase and tensin homolog abolished the JNK-mediated effects on Akt activity, indicating that phosphatase and tensin homolog mediates crosstalk between these pathways. Conclusions - Loss of Jnk1, but not Jnk2, in macrophages protects them from apoptosis, increasing cell survival, and this accelerates early atherosclerosis.
Open Access
Model based analysis of the variation in Korotkoff sound onset time during exercise
(Institute of Physics Publishing, 2001) Türkmen, A.; Ider, Y. Z.
In this study, a minimal mathematical model of the cardiovascular system is used to study the effects of changes in arterial compliance and cardiac contractility on the onset time of Korotkoff sounds during an auscultatory procedure. The model provides blood pressure waveforms in the ventricle, the aorta and the brachial artery. From these waveforms, pre-ejection time, pulse propagation time and rise time of the blood pressure at the brachial artery can be computed. The time delay between onset time of ECG Q wave and onset time of Korotkoff sound is the sum of these three times. Rise time is zero and the time delay is minimal when the cuff pressure is slightly above the diastolic pressure. This minimum time delay is represented by QKD. Simulation results suggest that during the Bruce exercise protocol QKD decreases to one-third of its pre-exercise value if the cardiac contractility increases threefold. The effect of arterial compliance is not as significant as that of the cardiac contractility. From data recorded during an exercise test, it is observed that QKD decreases considerably as the test load is increased. We show in this study that the amount of decrease in QKD can be used as an index of the amount of increase in cardiac contractility during an exercise ECG test. Use of signal averaging for reducing the effect of motion artifacts during an exercise test is also shown to be very instrumental for making accurate QKD measurements.