Publications by authors named "Melanie Cruz Santos"
Background: Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in the ECM (extracellular matrix) and cardiomyocyte structure. These alterations critically contribute to impaired contractility and relaxation, ultimately leading to heart failure. Emerging evidence implicates that extracellular signaling molecules are critically involved in the pathogenesis of cardiac hypertrophy and remodeling.
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- The study investigates the role of Na+-activated Slack potassium channels in regulating neuronal and cardiovascular activity, particularly during ischemia and reperfusion (I/R) injury.
- Researchers found that Slack channels are essential for K+ currents in cardiomyocytes and help prevent excessive Ca2+ accumulation, which can lead to cell death under low oxygen conditions.
- The findings emphasize Slack's critical role in maintaining ion balance in heart cells, suggesting that its activity may protect against cardiac damage during I/R injuries.
Mutations of large conductance Ca- and voltage-activated K channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL).
View Article and Find Full Text PDF3',5'-cyclic guanosine monophosphate (cGMP) is a druggable second messenger regulating cell growth and survival in a plethora of cells and disease states, many of which are associated with hypoxia. For example, in myocardial infarction and heart failure (HF), clinical use of cGMP-elevating drugs improves disease outcomes. Although they protect mice from ischemia/reperfusion (I/R) injury, the exact mechanism how cardiac cGMP signaling is regulated in response to hypoxia is still largely unknown.
View Article and Find Full Text PDFThe cysteine-rich LIM-only protein 4 (CRP4), a LIM-domain and zinc finger containing adapter protein, has been implicated as a downstream effector of the second messenger 3',5'-cyclic guanosine monophosphate (cGMP) pathway in multiple cell types, including vascular smooth muscle cells (VSMCs). VSMCs and nitric oxide (NO)-induced cGMP signaling through cGMP-dependent protein kinase type I (cGKI) play fundamental roles in the physiological regulation of vascular tone and arterial blood pressure (BP). However, it remains unclear whether the vasorelaxant actions attributed to the NO/cGMP axis require CRP4.
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- - The 3',5'-cGMP pathway enhances the survival of heart cells during ischaemia and reperfusion injury by triggering protective responses, primarily through nitric oxide (NO)-sensitive guanylate cyclase (GC) which leads to cGMP production.
- - The activation of cGMP-dependent protein kinase I (cGKI) by cGMP results in the phosphorylation of various substrates, promoting the opening of mitochondrial ATP-sensitive potassium channels (mitoK) and BK-type calcium-activated potassium channels (mitoBK).
- - Agents that activate mitoK or mitoBK can help protect against damage caused by ischemia and reperfusion, suggesting that the relationship between the cGMP pathway and these