[PDF] The Role Of Collagen In Cardiac Mechanics And Adverse Left Ventricle Remodeling Post Myocardial Infarction eBook

Author : Andrew Voorhees
Publisher :
Page : 148 pages
File Size : 14,45 MB
Release : 2014
Category :
ISBN : 9781321475173

GET BOOK

Myocardial infarction (MI) occurs when the coronary arteries that supply blood to the myocardial tissue of the heart become blocked, triggering a dynamic wound healing response and eventually leading to the formation of a collagen rich scar tissue. The properties of the collagen network that forms dictate the mechanical behavior of the infarct tissue, which in turn alters the pumping function of the left ventricle (LV). However, little is known about how variations in the collagen network alter the function of the LV and contribute to differences in patient outcome. The goal of this dissertation is to clarify the mechanisms by which variation in the structural properties of the collagen network affect the mechanical properties of the infarct tissue and the pumping function of the LV through both computational and experimental approaches. The computational approach identified that a longitudinal alignment of collagen fibers in the infarct region is able to both maximize distension of the LV during diastolic filling and the contractile force generated by the healthy regions of the LV through the Frank-Starling mechanism. The experimental approach revealed a novel mechanism to reduce LV dilation by facilitating the assembly and cross-linking of collagen fibers through deletion of the gene for matrix metalloproteinase-9. This was the first study to quantify infarct mechanical properties in mice. This work opens up new areas for potential research and the findings may lead to the development of new diagnostic and therapeutic technologies.

Author : Gabriel Grilo
Publisher :
Page : 109 pages
File Size : 49,68 MB
Release : 2020
Category :
ISBN :

GET BOOK

Cardiac remodeling is composed of molecular, cellular, and interstitial changes in the cardiac tissue that affect the size, shape, and function of the heart. There are two types of cardiac remodeling: physiological and pathological remodeling. Physiological remodeling of the heart is an adaptation of the organ based on the body's demand, such as changes due to physical exercises and during aging. Cardiac pathological remodeling can occur due to the evolution of a chronic disorder in the cardiovascular system or after an acute injury, such as myocardial infarction (MI). In this thesis, we investigated both physiological and pathological cardiac remodeling, with particular focus on the role of the extracellular matrix (ECM). Determining the mechanisms involved in cardiac remodeling by changes in ECM provides insight to distinguish the local and functional changes from external risk factors; and it provides identification of novel targets that could be used as therapeutic approaches to reduce cardiac dysfunction. In our first study, we hypothesized that changes in ECM composition during physiological remodeling with age occurs in a sex-specific manner, since cardiac function varies between sexes among cardiovascular disease patients. We assessed cardiac parameters using both conventional echocardiography and speckle tracking echocardiography (STE). Our results suggest that STE allows for early detection of changes in cardiac function between sexes during aging. ECM factors involved in collagen metabolism, such as decorin, osteopontin, Cthrc1, and Ddr1 expression were age-dependent but sex-independent; while periostin, lysyl oxidase, and Mrc2 displayed age-dependent and sex specific differences. These data highlight the importance of including sex-differences analysis when studying cardiac aging. In our second study, we investigated the role of a collagen-derived matricryptin in pathological remodeling. Matricryptins are biologically active peptides, generated from ECM proteolysis, able to regulate cell function and survival. We tested the potential of the matricryptin p1159 to reduce adverse cardiac remodeling using a rodent MI model. A previous study from our lab showed that p1159 plasma levels negatively correlate with left ventricle (LV) filling pressure, suggesting a beneficial role against adverse remodeling. In this thesis, we found that p1159 increases cardiac fibroblast migration by activating RhoA pathways via the membrane receptor integrin alpha 4. Fibroblast migration is an essential step during cardiac healing. In addition, p1159 significantly improved cardiac function post-MI by inducing the formation of a compliant and organized infarct scar, which promoted LV contractility and preserved the structural integrity of the heart. Our data strongly supports matricryptin p1159 as a therapeutic treatment to reduce adverse remodeling post-MI.

Author : Bodh I. Jugdutt
Publisher : Springer Science & Business Media
Page : 566 pages
File Size : 43,42 MB
Release : 2013-02-15
Category : Medical
ISBN : 1461459303

GET BOOK

The main objective of Cardiac Remodeling: Molecular Mechanisms is to summarize the major research advances in molecular, biochemical and translational aspects of cardiac remodeling over the last 2 to 3 decades under one cover and touch on future directions. It provides a high profile and valuable publication resource on molecular mechanisms of cardiac remodeling for both the present and future generations of researchers, teachers, students and trainees. This book should stimulate future translational research targeted towards discovery and development for preventing, limiting and reversing bad remodeling over the next few decades, with the ultimate goal of preventing progression to systolic and/or diastolic heart failure. The chapters suggest potential novel strategies that should receive attention for translating basic research knowledge to application in patients at the bedside.

Author : Pawan K. Singal
Publisher : Springer Science & Business Media
Page : 570 pages
File Size : 34,78 MB
Release : 2012-12-06
Category : Medical
ISBN : 1441992626

GET BOOK

According to the World Health Report (2000 http:/ /www. who. int/whr), of the 55 million deaths worldwide in 1999, more than 16 million were secondary to car diovascular complications. With the prospect of world population increasing from the current level of 6 billion to 9 billion by the middle of this century, the burden of cardiac disease is going to increase astronomically. Furthermore, scientists are being challenged not only to reduce mortality, but also to improve quality of life. Thus, more than ever, intellectuals from different disciplines including biology, sociology, informatics and health care have to join forces to meet the mandate. The World Heart Congress with a focus on "Frontiers in Cardiovascular Health" held in Winnipeg during July 6-11, 2001, made a unique attempt to bring these specialists together to brainstorm and map out the course of action for cardiovascular research and health in the next century. Anytime there is a relative increase in the workload on the heart, there are adap tive myocardial as well as humoral responses. When these adaptations or remodel ing at the organ, subcellular or gene level, become inadequate for a proper tissue perfusion, the condition of heart failure ensues. Prevention of the factors leading to the relative increase in workload as well as a better understanding of the adap tive responses and their failure are some of the hopes to combat the morbidity and mortality due to heart failure.

Author : Jennifer Elaine Naugle
Publisher :
Page : 152 pages
File Size : 16,24 MB
Release : 2006
Category : Collagen
ISBN :

GET BOOK

Cardiac fibroblasts (CFs) are the major non-contractile cells present in the myocardium, and are primary regulators of synthesis and secretion of extracellular matrix (ECM) proteins. Both proliferation and differentiation of CFs can potentially result in excess ECM protein production and cardiac fibrosis, a condition characterized by a stiffening of the myocardium. This condition is common after myocardial infarction and develops during heart failure, resulting in compromised cardiac function. Hormonal input, as well as input from the surrounding ECM can affect CF proliferation and/or differentiation, and an increase in either one of these parameters will result in elevated ECM production. Consequently, limiting prolonged fibroblast activation and the subsequent detrimental ECM production after myocardial infarction or heart failure might help to preserve left ventricular function. The specific ECM composition in the myocardium likely imparts significant effects on CF function. However, to date little is known about the effect of the ECM on CF function or the signaling pathways utilized by ECM molecules. In the adult, the myocardium is primarily composed of types I and III collagen, in addition to lower levels of types IV, V, and VI collagen. Extensive remodeling of the ECM occurs following myocardial infarction, and the resulting ECM composition can influence cardiac fibroblast activation in addition to affecting cardiac performance. My goals are to determine the mechanism of Gq/Gs cross-talk and the functional consequences in CFs, to determine the functional effects of specific types of collagen on CF differentiation and proliferation, and to identify the collagen composition and myofibroblast content post-myocardial infarction.

Author : Zhijie Wang
Publisher :
Page : 0 pages
File Size : 26,16 MB
Release : 2019
Category : Science
ISBN :

GET BOOK

The extracellular matrix (ECM) forms a mesh surrounding tissue, made up of fibrous and non-fibrous proteins that contribute to the cellular function, mechanical properties of the tissue and physiological function of the organ. The cardiac ECM remodels in response to mechanical alterations (e.g., pressure overload, volume overload) or injuries (e.g., myocardial infarction, bacterial infection), which further leads to mechanical and functional changes of the heart. Collagen, the most prevalent ECM protein in the body, contributes significantly to the mechanical behavior of myocardium during disease progression. Alterations in collagen fiber morphology and alignment, isoform, and cross-linking occur during the progression of various cardiac diseases. Acute or compensatory remodeling of cardiac ECM maintains normal cardiac function. However, chronic or decompensatory remodeling eventually results in heart failure, and the exact mechanism of transition into maladaptation remains unclear. This review aims to summarize the primary role of collagen accumulation (fibrosis) in heart failure progression, with a focus on its effects on myocardial tissue mechanical properties and cellular and organ functions.

Author : Sarah Joan Margaret McLaughlin
Publisher :
Page : pages
File Size : 37,36 MB
Release : 2021
Category :
ISBN :

GET BOOK

Myocardial infarction (MI) leads to permanent loss of cardiac muscle due to the limited regenerative potential of the mammalian heart. The affected heart muscle is replaced by a fibrotic scar; however, the scar is not able to offset the increase in wall stress placed on the remaining myocardium. This distending pressure can lead to dilative remodeling of the ventricle, progressive loss of cardiac function, and heart failure. Despite current medical therapy, heart failure continues to have a high mortality rate. Therefore, there is a clinical need for treatments that can both improve cardiac function post-MI and reduce ventricular remodeling to prevent progression to heart failure. Injectable biomaterials aim to provide a scaffold to stimulate infarct repair by mimicking the healthy cardiac extracellular matrix (ECM). The ECM plays a critical role in tissue regeneration but after a MI it is pathologically modified. Injection of biomaterials post-MI can provide a scaffold that better stimulates infarct repair. In this study, hydrogels were developed from recombinant human type I and type III collagen (rHCI and rHCIII), the two most prevalent structural proteins in the cardiac ECM. Injection of rHCI and rHCIII hydrogels in a mouse model of MI improved cardiac function and reduced infarct size 28 days post-treatment. Infarcted hearts treated with rHCI exhibited improved myocardial salvage in the region bordering the scar with improved capillary density. rHCI hydrogel was also superior to rHCIII in reducing ventricular remodeling. The injection of rHCI hydrogel into the border zone post-MI resulted in an acute improvement of contractile function two days after treatment that was maintained long-term. At two days post-injection, rHCI treated animals had reduced apoptotic cardiomyocytes and lower levels of oxidative stress. Methylglyoxal modifies and crosslinks collagen in the ECM, leading to oxidative stress. Two days after injection, the rHCI hydrogel at the epicardial surface was modified by methylglyoxal, while methylglyoxal-derived advanced glycation end-product levels in the underlying myocardium were lower than in control animals. It appears that rHCI hydrogel injection is soaking up free methylglyoxal from the myocardium, reducing levels of oxidative stress in cardiac muscle and improving contractility of cardiomyocytes bordering the scar. These results suggest that rHC therapy is a promising approach to improve cardiac contractility, and limit ventricular remodeling post-MI.