99 research outputs found
Gene Expression, Function and Ischemia Tolerance in Male and Female Rat Hearts After Sub-Toxic Levels of Angiotensin II
To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litterāmatched rats were treated with 400Ā ngĀ kgā1Ā minā1 Ang II for 14Ā days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, Ī²-MCH, Ankrd-1, PKC-Ī±, PKC-Ī“ TNF-Ī±); fibrosis (Col I-Ī±1, Col III-Ī±1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response
Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless āFrankāStarling Gainā index
This paper briefly recapitulates the FrankāStarling law of the heart, reviews approaches to establishing diastolic and systolic forceālength behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called āFrankāStarling Gainā, calculated as the ratio of slopes of end-systolic and end-diastolic forceālength relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the FrankāStarling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties
A Unique Role for Nonmuscle Myosin Heavy Chain IIA in Regulation of Epithelial Apical Junctions
The integrity and function of the epithelial barrier is dependent on the apical junctional complex (AJC) composed of tight and adherens junctions and regulated by the underlying actin filaments. A major F-actin motor, myosin II, was previously implicated in regulation of the AJC, however direct evidence of the involvement of myosin II in AJC dynamics are lacking and the molecular identity of the myosin II motor that regulates formation and disassembly of apical junctions in mammalian epithelia is unknown. We investigated the role of nonmuscle myosin II (NMMII) heavy chain isoforms, A, B, and C in regulation of epithelial AJC dynamics and function. Expression of the three NMMII isoforms was observed in model intestinal epithelial cell lines, where all isoforms accumulated within the perijunctional F-actin belt. siRNA-mediated downregulation of NMMIIA, but not NMMIIB or NMMIIC expression in SK-CO15 colonic epithelial cells resulted in profound changes of cell morphology and cell-cell adhesions. These changes included acquisition of a fibroblast-like cell shape, defective paracellular barrier, and substantial attenuation of the assembly and disassembly of both adherens and tight junctions. Impaired assembly of the AJC observed after NMMIIA knock-down involved dramatic disorganization of perijunctional actin filaments. These findings provide the first direct non-pharmacological evidence of myosin II-dependent regulation of AJC dynamics in mammalian epithelia and highlight a unique role of NMMIIA in junctional biogenesis
Advancing Precision Medicine for Alcohol Use Disorder: Replication and Extension of Reward Drinking as a Predictor of Naltrexone Response
Five Priority Areas for Improving Medications Development for Alcohol Use Disorder and Promoting Their Routine Use in Clinical Practice
Mechanical properties and ATPase activity in glycerinated cardiac muscle of hyperthyroid rabbit
Myosin Heavy Chain Isoform Patterns Do Not Correlate with Force-Velocity Relationships in Pulmonary Arterial Compared with Systemic Arterial Smooth Muscle
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