Cell Stress Response Normal Heart Failure





Fig. 4.8 Expression arrays are also useful to determine host stress response signaling pathways in the presence of heart failure. In this experiment, we can see that intracellular cytokine signaling path ways of Ick and fyn are both up regulated in the setting of heart failure. This is consistent with the activation of cytokine and immune signaling pathways in the setting of heart failure.

this technology to systematically identify novel ethology specific markers of disease.

This strategy has also been recently employed in prostatic cancer, where early and accurate diagnosis is particularly useful for determining course of action. Using microarray methods, an early diagnostic pattern was indeed recognized, two signaling molecules appear to be unique to early prostatic cancer - hepsin and pim-1, both are serine-threonine kinases [31].

In addition, with the increasing utilization of ventricular assist devices, there is access to tissues from heart failure patients has improved. In addition, gathering data has now become available on the potential changes and reversibility of the abnormalities observed in heart failure, and the opportunity of using this information in the future for prognosis of the patients, and in turn determining which patient may come off the assist device support, and which patient will need heart transplantation.


Application: Therapeutic Insights

How a drug acomplishes its therapeutic effect in the clinical setting has always been difficult. A drug may be developed for the purpose of targeting a specific pathway. However, in many occasions, it is the unintended effects of a drug that ultimately determine its overall biological profile in the clinical setting. An example is the recent publication of the effect of beta blockers in the setting to understand heart failure. It appears that only in patients when the beta blockade can alter the cardiac contractile protein such as the myosin isoforms that the patient will benefit with respect to reverse remodeling and improvement in clinical outcome. Therefore the availability of microarrays will now offer an unprecedented opportunity to define the diverse targets that are affected by a certain therapeutic intervention, and define the true biological impact of a certain treatment strategy. This will be particularly important in the setting of heart failure, involving a large complex of pathophysiological pathways.



The work is supported in part by grants from the Heart and Stroke Foundation of Ontario, and the Canadian Institutes of Health Research (CIHR).



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