Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells

Kavanagh, Dean; Lokman, Adam; Neag, Georgiana; Colley, Abigail; Kalia, Neena

doi:10.1093/cvr/cvz118

Cited by 25 publications

(23 citation statements)

References 48 publications

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“…Using similar passive motion stabilizers, prospective and retrospective image gating methods have been incorporated to image with high resolution (71) however, image gating fails to capture the dynamics of the heart at its peak contraction (systole). Recently, Kavanagh et al have applied passive tissue stabilization of the beating heart without gating strategies, using fluorophore-conjugated antibodies to visualize neutrophils and platelets following ischemia-reperfusion injury (72).…”

Section: Intravital Imaging Of Leukocytes In the Heart: Previous Apprmentioning

confidence: 99%

Intravital Microscopy of the Beating Murine Heart to Understand Cardiac Leukocyte Dynamics

et al. 2020

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Cardiovascular disease is the leading cause of worldwide mortality. Intravital microscopy has provided unprecedented insight into leukocyte biology by enabling the visualization of dynamic responses within living organ systems at the cell-scale. The heart presents a uniquely dynamic microenvironment driven by periodic, synchronous electrical conduction leading to rhythmic contractions of cardiomyocytes, and phasic coronary blood flow. In addition to functions shared throughout the body, immune cells have specific functions in the heart including tissue-resident macrophage-facilitated electrical conduction and rapid monocyte infiltration upon injury. Leukocyte responses to cardiac pathologies, including myocardial infarction and heart failure, have been well-studied using standard techniques, however, certain questions related to spatiotemporal relationships remain unanswered. Intravital imaging techniques could greatly benefit our understanding of the complexities of in vivo leukocyte behavior within cardiac tissue, but these techniques have been challenging to apply. Different approaches have been developed including high frame rate imaging of the beating heart, explantation models, micro-endoscopy, and mechanical stabilization coupled with various acquisition schemes to overcome challenges specific to the heart. The field of cardiac science has only begun to benefit from intravital microscopy techniques. The current focused review presents an overview of leukocyte responses in the heart, recent developments in intravital microscopy for the murine heart, and a discussion of future developments and applications for cardiovascular immunology.

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Section: Intravital Imaging Of Leukocytes In the Heart: Previous Apprmentioning

confidence: 99%

Intravital Microscopy of the Beating Murine Heart to Understand Cardiac Leukocyte Dynamics

et al. 2020

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“…Areas of “no-reflow” are shown with white arrows. Figures adapted from published figure (68) (scale bar: 100 μm). (C) Using a combination of vascular contrast agents and cellular staining, cell trafficking in and out of vessels can be examined in depth.…”

Section: Confocal and Multiphoton Intravital Imaging Of The Beating Hmentioning

confidence: 99%

“…This effect leads to an increased background signal on spinning disk confocal microscopy when compared to laser scanning confocal. However, the speed advantages gained from employing spinning disk confocal has allowed some labs—including ours—to perform cardiac intravital without necessarily needing aggressive post-analysis image restoration techniques (68).…”

Section: Confocal and Multiphoton Intravital Imaging Of The Beating Hmentioning

confidence: 99%

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Live Intravital Imaging of Cellular Trafficking in the Cardiac Microvasculature—Beating the Odds

Kavanagh

Kalia

2019

Front. Immunol.

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Although mortality rates from cardiovascular disease in the developed world are falling, the prevalence of cardiovascular disease (CVD) is not. Each year, the number of people either being diagnosed as suffering with CVD or undergoing a surgical procedure related to it, such as percutaneous coronary intervention, continues to increase. In order to ensure that we can effectively manage these diseases in the future, it is critical that we fully understand their basic physiology and their underlying causative factors. Over recent years, the important role of the cardiac microcirculation in both acute and chronic disorders of the heart has become clear. The recruitment of inflammatory cells into the cardiac microcirculation and their subsequent activation may contribute significantly to tissue damage, adverse remodeling, and poor outcomes during recovery. However, our basic understanding of the cardiac microcirculation is hampered by an historic inability to image the microvessels of the beating heart—something we have been able to achieve in other organs for over 100 years. This stems from a couple of clear and obvious difficulties related to imaging the heart—firstly, it has significant inherent contractile motion and is affected considerably by the movement of lungs. Secondly, it is located in an anatomically challenging position for microscopy. However, recent microscopic and technological developments have allowed us to overcome some of these challenges and to begin to answer some of the basic outstanding questions in cardiac microvascular physiology, particularly in relation to inflammatory cell recruitment. In this review, we will discuss some of the historic work that took place in the latter part of last century toward cardiac intravital, before moving onto the advanced work that has been performed since. This work, which has utilized technology such as spinning-disk confocal and multiphoton microscopy, has—along with some significant advancements in algorithms and software—unlocked our ability to image the “business end” of the cardiac vascular tree. This review will provide an overview of these techniques, as well as some practical pointers toward software and other tools that may be useful for other researchers who are considering utilizing this technique themselves.

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“…[ 8 ] Continuous superimpositon of thrombi at the site of atherosclerosis and a large number of thrombi formed in downstream functional capillaries narrow the remaining vascular lumen, thus seriously affecting blood supply of the myocardial tissue. [ 9 ] These may also be the reason why the targeted modified NPs are still difficult to be delivered to the target site in vivo, although they exhibited high targeting and transfection efficiency in vitro. [ 10 ] This difficulty can be partially reflected by the weak accumulation of micro‐RNA within the infarct of MI.…”

Section: Introductionmentioning

confidence: 99%

A Novel Anti‐Coagulative Nanocomplex in Delivering miRNA‐1 Inhibitor Against Microvascular Obstruction of Myocardial Infarction

Hong

Wei

Xue

et al. 2020

Adv Healthcare Materials

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Great progress has been made in miRNA nanodelivery for the treatment of myocardial infarction (MI). However, miRNA nanodelivery within the infarct is impeded by microvascular obstruction as a local circulatory disorder caused by microthrombus formation in microvessels. Knowing that low molecular weight heparin (LMWH) can effectively prevent microthrombus formation in microcirculation, it is hypothesized whether surface modification of the nanocarrier with LMWH can overcome microvascular obstruction in the infarct area for better miRNA delivery. Herein, a novel nanocomlex consisting of dendrigraft poly‐l‐lysine (DGL)‐loaded miR‐1 inhibitor as the core to decrease apoptosis of cardiomyocytes and LMWH as the shell to overcome microvascular obstruction of the infarct area is developed. The results show that this anti‐coagulative nanocomlex is able to reduce microthrombus formation in microvessels and inhibit blood‐coagulation factor Xa, thereby overcoming microvascular obstruction in the infarct area. In addition, it further enhances the uptake of miR‐1 inhibitor within the infarct and decreases myocardiocyte apoptosis, thus improving the cardiac function and attenuating the myocardial fibrosis. In conclusion, modification of DGL‐loaded miR‐1 inhibitor with LMWH helps overcome microvascular obstruction in delivering the drug to the infarct area, thus providing a promising therapeutic strategy for achieving a better therapeutic outcome of MI.

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Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells

Cited by 25 publications

References 48 publications

Intravital Microscopy of the Beating Murine Heart to Understand Cardiac Leukocyte Dynamics

Intravital Microscopy of the Beating Murine Heart to Understand Cardiac Leukocyte Dynamics

Live Intravital Imaging of Cellular Trafficking in the Cardiac Microvasculature—Beating the Odds

A Novel Anti‐Coagulative Nanocomplex in Delivering miRNA‐1 Inhibitor Against Microvascular Obstruction of Myocardial Infarction

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