Microcirculatory dysfunction in the heart and the brain

Mejía‐Rentería, Hernán; Matías‐Guiu, Jordi A.; Lauri, Francesco; Yus, Miguel; Escaned, Javier

doi:10.23736/s0026-4725.18.04701-1

Cited by 13 publications

(6 citation statements)

References 93 publications

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“…Cerebral SVD has been associated to a variety of brain parenchyma structural alterations, including WMH, micro-hemorrhages, disruption of myelin, lacunae, dilated perivascular spaces, reduced glial and neuronal density (19). Pathological analysis of the small arteries associated with these alterations has showed loss of smooth muscle cells from the tunica media, with thickening of the vessel wall due fibro-hyalinosis, similar to what is encountered in CMD (19,20). Microatheroma has been reported in earlier pathological reports though now is not common.…”

Section: I S C L a I M E R : T H E M A N U S C R I P T A N D I T S C O N T E N T S A R E C O N F I D E N T I A L I N T E N D E D F O R Jmentioning

confidence: 92%

Association of White Matter Hyperintensities and Cardiovascular Disease

Moroni

Ammirati

Hainsworth

et al. 2020

Circ: Cardiovascular Imaging

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Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue perfusion through an intricate network of penetrating small vessels. Both organs rely on fine tuning of local blood flow to match metabolic demand. Blood flow regulation requires adequate functioning of the microcirculation in both organs, with loss of microvascular function, termed small vessel disease (SVD) underlying different potential clinical manifestations. SVD in the heart, known as coronary microvascular dysfunction, can cause chronic or acute myocardial ischemia and may lead to development of heart failure. In the brain, cerebral SVD can cause an acute stroke syndrome known as lacunar stroke or more subtle pathological alterations of the brain parenchyma, which may eventually lead to neurological deficits or cognitive decline in the long term. Coronary microcirculation cannot be visualized in vivo in humans, and functional information can be deduced by measuring the coronary flow reserve. The diagnosis of cerebral SVD is largely based on brain magnetic resonance imaging, with white matter hyperintensities, microbleeds, and brain atrophy reflecting key structural changes. There is evidence that such structural changes reflect underlying cerebral SVD. Here, we review interactions between SVD and cardiovascular risk factors, and we discuss the evidence linking cerebral SVD with large vessel atheroma, atrial fibrillation, heart failure, and heart valve disease.

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Section: I S C L a I M E R : T H E M A N U S C R I P T A N D I T S C O N T E N T S A R E C O N F I D E N T I A L I N T E N D E D F O R Jmentioning

confidence: 92%

Association of White Matter Hyperintensities and Cardiovascular Disease

Moroni

Ammirati

Hainsworth

et al. 2020

Circ: Cardiovascular Imaging

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“…Another potential cause is that LVAD with non‐pulsatile flow may have triggered further changes in a pre‐existing imbalance between the microcirculation of the heart and peripheral and cerebral circulation. 22 Consequently, PI values may have solely reflected these processes responsible for subsequent clinical events.…”

Section: Discussionmentioning

confidence: 99%

Increased pulsatility index is associated with adverse outcomes in left ventricular assist device recipients

et al. 2021

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Aims Recipients of left ventricular assist devices (LVAD) are exposed to increased risk of adverse clinical events. One of the potential contributing factors is non-pulsatile flow generated by LVAD. We evaluated the association of flow patterns in carotid arteries and of increased arterial stiffness with death and cerebrovascular events in LVAD recipients. Methods and resultsWe analysed data from 83 patients [mean age 54 ± 15 years; 12 women; HeartMate II (HMII), n = 34; HeartMate 3 (HM3), n = 49]. Pulsatile and resistive indexes, atherosclerotic changes in carotid arteries (measured by duplex ultrasound), and arterial stiffness [measured by Endo-PAT 2000 as the augmentation index standardized for heart rate (AI@75)] were evaluated 3 and 6 months after LVAD implantation. Sixteen patients died during follow-up (27.3 months; interquartile range 15.7-44.3). After adjusting for the main variables examined, the pulsatility index measured at 3 months was positively associated with increased hazard ratios (HR) for death and cerebrovascular events [HR 9.8, 95% confidence interval (CI) 1.62-59.42], with HR increasing after adding AI@75 to the model (HR 18.8, 95% CI 2.44-145.50). In HM3 recipients, HR was significantly lower than in HMII recipients (HR 0.31, 95% CI 0.11-0.91), but the significance disappeared after adding AI@75 to the model (HR 0.33, 95% CI 0.09-1.18). Conclusions The risk of death and cerebrovascular events in LVAD recipients is associated with increased pulsatility index in carotid arteries and potentiated by increased arterial stiffness. The same risk is attenuated by HM3 LVAD implantation, but this effect is weakened by increased arterial stiffness.

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“…These molecules already represent therapeutic targets in various treatment regimens including atherosclerosis, rheumatoid arthritis, Crohn’s disease, psoriasis, deep vein thrombosis, pulmonary embolism, and malignant cancers ( Arroyo and Iruela-Arispe, 2010 ; Ridker et al, 2017a ; Ridker et al, 2017b ; Mitoma et al, 2018 ; Ridker et al, 2018 ; Jackson et al, 2019 ; Libby and Everett, 2019 ; Ridker, 2019 ). Regression of blood capillaries has been identified as pathogenically linked to hypertension, renal ischemic injury, aging, and neurodegeneration, and may be a critical pathogenic feature of many other major human diseases ( Noon et al, 1997 ; Basile, 2004 ; Battegay et al, 2007 ; Sim et al, 2014 ; Tibirica et al, 2015 ; Manukhina et al, 2016 ; Hinkel et al, 2017 ; Mejia-Renteria et al, 2019 ; Yeung et al, 2019 ; Zeng and Chen, 2019 ). It is becoming increasingly evident that we need to better understand the cell biology of both lymphatic and blood capillaries, as these two types of capillary networks fundamentally support and affect each other.…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory mediators, TNFα, IFNγ, and thrombin, directly induce lymphatic capillary tube regression

Kemp

Penn

Koller

et al. 2022

Front. Cell Dev. Biol.

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In this work, we sought to investigate the direct effects of proinflammatory mediators on lymphatic endothelial cell (LEC) capillaries and whether they might induce regression. Our laboratory has developed novel in-vitro, serum-free, lymphatic tubulogenesis assay models whereby human LEC tube networks readily form in either three-dimensional collagen or fibrin matrices. These systems were initially conceptualized in the hopes of better understanding the influence of proinflammatory mediators on LEC capillaries. In this work, we have screened and identified proinflammatory mediators that cause regression of LEC tube networks, the most potent of which is TNFα (tumor necrosis factor alpha), followed by IFNγ (interferon gamma) and thrombin. When these mediators were combined, even greater and more rapid lymphatic capillary regression occurred. Surprisingly, IL-1β (interleukin-1 beta), one of the most potent and pathologic cytokines known, had no regressive effect on these tube networks. Finally, we identified new pharmacological drug combinations capable of rescuing LEC capillaries from regression in response to the potent combination of TNFα, IFNγ, and thrombin. We speculate that protecting lymphatic capillaries from regression may be an important step toward mitigating a wide variety of acute and chronic disease states, as lymphatics are believed to clear both proinflammatory cells and mediators from inflamed and damaged tissue beds. Overall, these studies identify key proinflammatory mediators, including TNFα, IFNγ, and thrombin, that induce regression of LEC tube networks, as well as identify potential therapeutic agents to diminish LEC capillary regression responses.

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Microcirculatory dysfunction in the heart and the brain

Cited by 13 publications

References 93 publications

Association of White Matter Hyperintensities and Cardiovascular Disease

Association of White Matter Hyperintensities and Cardiovascular Disease

Increased pulsatility index is associated with adverse outcomes in left ventricular assist device recipients

Proinflammatory mediators, TNFα, IFNγ, and thrombin, directly induce lymphatic capillary tube regression

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