scholarly journals Mechanobiology of Microvascular Function and Structure in Health and Disease: Focus on the Coronary Circulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Maarten M. Brandt ◽  
Caroline Cheng ◽  
Daphne Merkus ◽  
Dirk J. Duncker ◽  
Oana Sorop
Keyword(s):  
Coronary Artery ◽  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Obstructive Coronary Artery Disease ◽  
Cardiac Activity ◽  
Myocardial Oxygen Demand ◽  
Mechanical Forces ◽  
Tight Coupling ◽  
Structural Alterations ◽  
Wide Range

The coronary microvasculature plays a key role in regulating the tight coupling between myocardial perfusion and myocardial oxygen demand across a wide range of cardiac activity. Short-term regulation of coronary blood flow in response to metabolic stimuli is achieved via adjustment of vascular diameter in different segments of the microvasculature in conjunction with mechanical forces eliciting myogenic and flow-mediated vasodilation. In contrast, chronic adjustments in flow regulation also involve microvascular structural modifications, termed remodeling. Vascular remodeling encompasses changes in microvascular diameter and/or density being largely modulated by mechanical forces acting on the endothelium and vascular smooth muscle cells. Whereas in recent years, substantial knowledge has been gathered regarding the molecular mechanisms controlling microvascular tone and how these are altered in various diseases, the structural adaptations in response to pathologic situations are less well understood. In this article, we review the factors involved in coronary microvascular functional and structural alterations in obstructive and non-obstructive coronary artery disease and the molecular mechanisms involved therein with a focus on mechanobiology. Cardiovascular risk factors including metabolic dysregulation, hypercholesterolemia, hypertension and aging have been shown to induce microvascular (endothelial) dysfunction and vascular remodeling. Additionally, alterations in biomechanical forces produced by a coronary artery stenosis are associated with microvascular functional and structural alterations. Future studies should be directed at further unraveling the mechanisms underlying the coronary microvascular functional and structural alterations in disease; a deeper understanding of these mechanisms is critical for the identification of potential new targets for the treatment of ischemic heart disease.

Gender Differences in Non-Obstructive Coronary Artery Disease

2020 ◽  
Vol 26 ◽  
Author(s):  
Maria Bergami ◽  
Marialuisa Scarpone ◽  
Edina Cenko ◽  
Elisa Varotti ◽  
Peter Louis Amaduzzi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Gender Differences ◽  
Heart Disease ◽  
Coronary Artery ◽  
Ischemic Heart Disease ◽  
Coronary Arteries ◽  
Obstructive Coronary Artery Disease ◽  
Ischemic Heart ◽  
Current Evidence ◽  
Artery Disease

: Subjects affected by ischemic heart disease with non-obstructive coronary arteries constitute a population that has received increasing attention over the past two decades. Since the first studies with coronary angiography, female patients have been reported to have non-obstructive coronary artery disease more frequently than their male counterparts, both in stable and acute clinical settings. Although traditionally considered a relatively infrequent and low-risk form of myocardial ischemia, its impact on clinical practice is undeniable, especially when it comes to infarction, where the prognosis is not as benign as previously assumed. Unfortunately, despite increasing awareness, there are still several questions left unanswered regarding diagnosis, risk stratification and treatment. The purpose of this review is to provide a state of the art and an update on current evidence available on gender differences in clinical characteristics, management and prognosis of ischemic heart disease with non-obstructive coronary arteries, both in the acute and stable clinical setting.

Myocardial Infarction in Systemic Lupus Erythematosus – the Sex Specific Risk Profile

2020 ◽  
Vol 26 ◽  
Author(s):  
Marija Vavlukis ◽  
Daniela Pop-Gjorceva ◽  
Lidija Poposka ◽  
Emilija Sandevska ◽  
Sasko Kedev
Keyword(s):  
Myocardial Infarction ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Young Women ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Systemic Lupus ◽  
Antiinflammatory Therapy

Background: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. Objective: The aim of this review is to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. Results: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and development of atherosclerosis at an earlier age. Contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3- fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or antiinflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. Conclusion: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although Systemic lupus erythematosus per se is a “female” disease, males are at increased cardiovascular risk and worse outcome. Method: We conducted a literature review through PubMed and Cochrane, using key words: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals OCT Findings in MINOCA

2021 ◽  
Vol 10 (13) ◽  
pp. 2759
Author(s):  
Krzysztof Bryniarski ◽  
Pawel Gasior ◽  
Jacek Legutko ◽  
Dawid Makowicz ◽  
Anna Kedziora ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Imaging Modality ◽  
Obstructive Coronary Artery Disease ◽  
Coronary Artery Spasm ◽  
Morphological Characteristics ◽  
Artery Dissection ◽  
Plaque Disruption ◽  
Artery Disease

Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is a working diagnosis for patients presenting with acute myocardial infarction without obstructive coronary artery disease on coronary angiography. It is a heterogenous entity with a number of possible etiologies that can be determined through the use of appropriate diagnostic algorithms. Common causes of a MINOCA may include plaque disruption, spontaneous coronary artery dissection, coronary artery spasm, and coronary thromboembolism. Optical coherence tomography (OCT) is an intravascular imaging modality which allows the differentiation of coronary tissue morphological characteristics including the identification of thin cap fibroatheroma and the differentiation between plaque rupture or erosion, due to its high resolution. In this narrative review we will discuss the role of OCT in patients presenting with MINOCA. In this group of patients OCT has been shown to reveal abnormal findings in almost half of the cases. Moreover, combining OCT with cardiac magnetic resonance (CMR) was shown to allow the identification of most of the underlying mechanisms of MINOCA. Hence, it is recommended that both OCT and CMR can be used in patients with a working diagnosis of MINOCA. Well-designed prospective studies are needed in order to gain a better understanding of this condition and to provide optimal management while reducing morbidity and mortality in that subset patients.

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

scholarly journals Genes encoding putative bicarbonate transporters as a missing molecular link between molt and mineralization in crustaceans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shai Abehsera ◽  
Shmuel Bentov ◽  
Xuguang Li ◽  
Simy Weil ◽  
Rivka Manor ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Molecular Mechanisms ◽  
Ph Control ◽  
Functional Genomic ◽  
Single Event ◽  
Tight Coupling ◽  
Molt Cycle ◽  
Mineral Deposition ◽  
Bicarbonate Transporters ◽  
Genes Encoding

AbstractDuring their life, crustaceans undergo several molts, which if theoretically compared to the human body would be equivalent to replacing all bones at a single event. Such a dramatic repetitive event is coupled to unique molecular mechanisms of mineralization so far mostly unknown. Unlike human bone mineralized with calcium phosphate, the crustacean exoskeleton is mineralized mainly by calcium carbonate. Crustacean growth thus necessitates well-timed mobilization of bicarbonate to specific extracellular sites of biomineralization at distinct molt cycle stages. Here, by looking at the crayfish Cherax quadricarinatus at different molting stages, we suggest that the mechanisms of bicarbonate ion transport for mineralization in crustaceans involve the SLC4 family of transporters and that these proteins play a key role in the tight coupling between molt cycle events and mineral deposition. This discovery of putative bicarbonate transporters in a pancrustacean with functional genomic evidence from genes encoding the SLC4 family—mostly known for their role in pH control—is discussed in the context of the evolution of calcium carbonate biomineralization.

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