scholarly journals Does the Heart Want What It Wants? A Case for Self-Adapting, Mechano-Sensitive Therapies After Infarction

2021 ◽  
Vol 8 ◽  
Author(s):  
William J. Richardson ◽  
Jesse D. Rogers ◽  
Francis G. Spinale
Keyword(s):  
Myocardial Infarction ◽  
Drug Targets ◽  
Scar Tissue ◽  
Alternative Approach ◽  
Self Tuning ◽  
Pharmacologic Effect ◽  
Do So ◽  
Spatial Needs

There is a critical need for interventions to control the development and remodeling of scar tissue after myocardial infarction. A significant hurdle to fibrosis-related therapy is presented by the complex spatial needs of the infarcted ventricle, namely that collagenous buildup is beneficial in the ischemic zone but detrimental in the border and remote zones. As a new, alternative approach, we present a case to develop self-adapting, mechano-sensitive drug targets in order to leverage local, microenvironmental mechanics to modulate a therapy's pharmacologic effect. Such approaches could provide self-tuning control to either promote fibrosis or reduce fibrosis only when and where it is beneficial to do so.

scholarly journals Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001614
Author(s):  
Mohammad R Ostovaneh ◽  
Raj R Makkar ◽  
Bharath Ambale-Venkatesh ◽  
Deborah Ascheim ◽  
Tarun Chakravarty ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trial ◽  
Myocardial Function ◽  
Randomised Clinical Trial ◽  
Scar Tissue ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Events ◽  
Lv Dysfunction ◽  
Registration Number

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups.ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

Identification of a circulating microvesicle protein network involved in ST-elevation myocardial infarction

2014 ◽  
Vol 112 (10) ◽  
pp. 716-726 ◽  
Author(s):  
Paula Vélez ◽  
Andrés Parguiña ◽  
Raymundo Ocaranza-Sánchez ◽  
Lilian Grigorian-Shamagian ◽  
Isaac Rosa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Protein Interactions ◽  
Drug Targets ◽  
Stable Coronary Artery Disease ◽  
Proteome Analysis ◽  
Open Reading Frames ◽  
St Elevation Myocardial Infarction ◽  
Α2 Macroglobulin ◽  
St Elevation ◽  
Promising Source

SummaryMembrane microvesicles (MVs) are released from activated cells, most notably platelets, into the circulation. They represent an important mode of intercellular communication, and their number is increased in patients with acute coronary syndromes. We present here a differential proteomic analysis of plasma MVs from ST-elevation myocardial infarction (STEMI) patients and stable coronary artery disease (SCAD) controls. The objective was the identification of MVs biomarkers/drug targets that could be relevant for the pathogenesis of the acute event. Proteome analysis was based on 2D-DIGE, and mass spectrometry. Validations were by western blotting in an independent cohort of patients and healthy individuals. A systems biology approach was used to predict protein-protein interactions and their relation with disease. Following gel image analysis, we detected 117 protein features that varied between STEMI and SCAD groups (fold change cut-off ≥2; p<0.01). From those, 102 were successfully identified, corresponding to 25 open-reading frames (ORFs). Most of the proteins identified are involved in inflammatory response and cardiovascular disease, with 11 ORFs related to infarction. Among others, we report an up-regulation of α2-macroglobulin isoforms, fibrinogen, and viperin in MVs from STEMI patients. Interestingly, several of the proteins identified are involved in thrombogenesis (e.g. α2-macroglobulin, and fibrinogen). In conclusion, we provide a unique panel of proteins that vary between plasma MVs from STEMI and SCAD patients and that might constitute a promising source of biomarkers/drug targets for myocardial infarction.

scholarly journals Practices of Piety: An Alternative Approach to the Study of Islamic Movements

Religions ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 520
Author(s):  
Aaron Rock-Singer
Keyword(s):  
Social Practice ◽  
Gender Segregation ◽  
Social Practices ◽  
Islamic Movements ◽  
Alternative Approach ◽  
And Performance ◽  
Do So

This article challenges the dominant organization-centered focus of the study of Islamic movements, and argues for a turn towards social practice. To do so, it traces the rise and spread of Egypt’s leading Salafi movement, Ansar al-Sunna al-Muhammadiyya (e. 1926) and its role in popularizing a series of distinct practices between 1940 and 1990. Based on the full run of this movement’s magazine, al-Hadi al-Nabawi (the Prophetic Guide, 1936–66) and al-Tawhid (Monolatry, 1973–93), the article explores the conditions in which practices such as praying in shoes and bareheaded, gender segregation and the cultivation of a fist-length beard were both politically viable and strategically advantageous. In doing so, it not only casts light on the trajectory of this movement, but also shows how and why the articulation and performance of distinct social practices are central to how Islamic movements shape society.

Layer-specific strain analysis: investigation of regional deformations in a rat model of acute versus chronic myocardial infarction

2012 ◽  
Vol 303 (5) ◽  
pp. H549-H558 ◽  
Author(s):  
Noa Bachner-Hinenzon ◽  
Offir Ertracht ◽  
Assaf Malka ◽  
Marina Leitman ◽  
Zvi Vered ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wall Thickness ◽  
Strain Analysis ◽  
Scar Tissue ◽  
The Other ◽  
Tissue Formation ◽  
Operating Characteristics ◽  
Specific Strain ◽  
Characteristics Analysis ◽  
Extent Of Damage

Myocardial infarction (MI) injury extends from the endocardium toward the epicardium. This phenomenon should be taken into consideration in the detection of MI. To study the extent of damage at different stages of MI, we hypothesized that measurement of layer-specific strain will allow better delineation of the MI extent than total wall thickness strain at acute stages but not at chronic stages, when fibrosis and remodeling have already occurred. After baseline echocardiography scans had been obtained, 24 rats underwent occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion. Thirteen rats were rescanned at 24 h post-MI and eleven rats at 2 wk post-MI. Next, rats were euthanized, and histological analysis for MI size was performed. Echocardiographic scans were postprocessed by a layer-specific speckle tracking program to measure the peak circumferential strain (SCpeak) at the endocardium, midlayer, and epicardium as well as total wall thickness SCpeak. Linear regression for MI size versus SCpeak showed that the slope was steeper for the endocardium compared with the other layers ( P < 0.001), meaning that the endocardium was more sensitive to MI size than the other layers. Moreover, receiver operating characteristics analysis yielded better sensitivity and specificity in the detection of MI using endocardial SCpeak instead of total wall thickness SCpeak at 24 h post-MI ( P < 0.05) but not 2 wk later. In conclusion, at acute stages of MI, before collagen deposition, scar tissue formation, and remodeling have occurred, damage may be nontransmural, and thus the use of endocardial SCpeak is advantageous over total wall thickness SCpeak.

Abstract 306: Loss of a Disintegrin and Metalloproteinase-15 Impairs Fibroblast Activation Following Myocardial Infarction Resulting in Ventricular Rupture

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Michael J Chute ◽  
Mengcheng Shen ◽  
Sayantan Jana ◽  
Wang Wang ◽  
Zamaneh Kassiri
Keyword(s):  
Myocardial Infarction ◽  
Second Harmonic ◽  
Healing Process ◽  
Cardiac Contractility ◽  
Scar Tissue ◽  
Wound Healing Process ◽  
Fibroblast Activation ◽  
Inflammatory Phase ◽  
A Disintegrin And Metalloproteinase

Background: Myocardial infarction (MI) occurs when blood flow to a region of the myocardium is interrupted. Over time, the damaged myocardium is replaced with scar tissue through activation of an inflammatory phase, followed by a reparative and a maturation phase. A disintegrin and metalloproteinase-15 (ADAM15) is a membrane-bound enzyme that is expressed in inflammatory cells and the heart, and its expression in the heart is increased following myocardial infarction. However, its function in heart disease has not yet been explored. We hypothesized that ADAM15 deficiency will impede the inflammatory response post-MI, which could reduce inflammation but also hinder scar formation causing adverse remodeling of the surviving myocardium. Methods: MI was induced in adult male wildtype (WT) and ADAM15-deficient ( Adam15 -/- ) mice by permanent ligation of the left anterior descending artery. LV structure, systolic and diastolic functions were assessed by echocardiography. Hearts were excised at 3-days or 1 week post-MI, processed for histological and molecular analyses. Fibrillar collagen organization was assessed by Second Harmonic Generation. Cardiac fibroblasts (cFBs) were isolated from WT or Adam15 -/- hearts, and subjected to ischemia (hypoxia + nutrient deletion) in vitro . Results: Adam15 -/- mice exhibited significantly compromised survival post-MI, mainly due to LV rupture. Cardiac contractility was reduced in Adam15 -/- compared to WT-MI mice. Collagen fibers in the scar tissue were distorted and scarce in Adam15 -/- MI hearts, associated with reduced levels of a major cross-linking enzyme, lysyl oxidase. In vitro, Adam15 -/- cFBs showed impaired myofibroblast transformation under ischemic conditions, suggesting attenuated fibroblast activation. Conclusion: Adam15 -deficiency impairs the wound healing process post-MI, leading to deleterious remodelling and LV rupture.

scholarly journals The zone of latent solutions and its relevance to understanding ape cultures

2020 ◽  
Vol 35 (5) ◽  
Author(s):  
Claudio Tennie ◽  
Elisa Bandini ◽  
Carel P. van Schaik ◽  
Lydia M. Hopper
Keyword(s):  
Social Learning ◽  
Null Hypothesis ◽  
Experimental Methodology ◽  
Great Ape ◽  
Cultural Patterns ◽  
Learning Mechanisms ◽  
New Approach ◽  
Learning Hypothesis ◽  
Alternative Approach ◽  
Do So

Abstract The zone of latent solutions (ZLS) hypothesis provides an alternative approach to explaining cultural patterns in primates and many other animals. According to the ZLS hypothesis, non-human great ape (henceforth: ape) cultures consist largely or solely of latent solutions. The current competing (and predominant) hypothesis for ape culture argues instead that at least some of their behavioural or artefact forms are copied through specific social learning mechanisms (“copying social learning hypothesis”) and that their forms may depend on copying (copying-dependent forms). In contrast, the ape ZLS hypothesis does not require these forms to be copied. Instead, it suggests that several (non-form-copying) social learning mechanisms help determine the frequency (but typically not the form) of these behaviours and artefacts within connected individuals. The ZLS hypothesis thus suggests that increases and stabilisations of a particular behaviour’s or artefact’s frequency can derive from socially-mediated (cued) form reinnovations. Therefore, and while genes and ecology play important roles as well, according to the ape ZLS hypothesis, apes typically acquire the forms of their behaviours and artefacts individually, but are usually socially induced to do so (provided sufficient opportunity, necessity, motivation and timing). The ZLS approach is often criticized—perhaps also because it challenges the current null hypothesis, which instead assumes a requirement of form-copying social learning mechanisms to explain many ape behavioural (and/or artefact) forms. However, as the ZLS hypothesis is a new approach, with less accumulated literature compared to the current null hypothesis, some confusion is to be expected. Here, we clarify the ZLS approach—also in relation to other competing hypotheses—and address misconceptions and objections. We believe that these clarifications will provide researchers with a coherent theoretical approach and an experimental methodology to examine the necessity of form-copying variants of social learning in apes, humans and other species.

Prevalence and functional impact of lipomatous metaplasia in scar tissue following myocardial infarction evaluated by MRI

2010 ◽  
Vol 20 (9) ◽  
pp. 2074-2083 ◽  
Author(s):  
Christian Lücke ◽  
Kathrin Schindler ◽  
Lukas Lehmkuhl ◽  
Matthias Grothoff ◽  
Ingo Eitel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Scar Tissue ◽  
Functional Impact ◽  
Lipomatous Metaplasia

scholarly journals Tissue distribution and transcriptional regulation of CCN5 in the heart after myocardial infarction

2021 ◽  
Author(s):  
Sima Zolfaghari ◽  
Ole Jørgen Kaasbøll ◽  
M. Shakil Ahmed ◽  
Fabian A. Line ◽  
Else Marie V. Hagelin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Tissue Distribution ◽  
Pressure Overload ◽  
Firefly Luciferase ◽  
Scar Tissue ◽  
Early Gene ◽  
Ccn Family ◽  
Protein Levels ◽  
Tnf Α

AbstractCCN5 is a divergent member of the cellular communication network factor (CCN) family in that it lacks the carboxyl terminal cystine knot domain common to the other CCN family members. CCN5 has been reported to antagonize the profibrotic actions of CCN2 and to inhibit myocardial collagen deposition and fibrosis in chronic pressure overload of the heart. However, what mechanisms that regulate CCN5 activity in the heart remain unknown. Recombinant, replication defective adenovirus encoding firefly luciferase under control of the human CCN5 promoter was prepared and used to investigate what mechanisms regulate CCN5 transcription in relevant cells. Tissue distribution of CCN5 in hearts from healthy mice and from mice subjected to myocardial infarction was investigated. Contrary to the profibrotic immediate early gene CCN2, we find that CCN5 is induced in the late proliferation and maturation phases of scar healing. CCN5 was identified principally in endothelial cells, fibroblasts, smooth muscle cells, and macrophages. Our data show that CCN5 gene transcription and protein levels are induced by catecholamines via β2-adrenergic receptors. Myocardial induction of CCN5 was further confirmed in isoproterenol-infused mice. We also find that CCN5 transcription is repressed by TNF-α, an inflammatory mediator highly elevated in early phases of wound healing following myocardial infarction. In conclusion, CCN5 predominates in endothelial cells, fibroblasts, and macrophages of the differentiating scar tissue and its transcription is conversely regulated by β2-adrenergic agonists and TNF-α.

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