The Role of Small Vessel Disease in Myocardial Infarction

Circulation ◽  
1969 ◽  
Vol 40 (5s4) ◽  
Author(s):  
THOMAS N. JAMES
Author(s):  
Rutger Heinen ◽  
Onno N. Groeneveld ◽  
Frederik Barkhof ◽  
Jeroen Bresser ◽  
Lieza G. Exalto ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1545
Author(s):  
Narek Manukjan ◽  
Zubair Ahmed ◽  
Daniel Fulton ◽  
W. Matthijs Blankesteijn ◽  
Sébastien Foulquier

Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC–OL crosstalk is essential in understanding cSVD development.


Neurology ◽  
2019 ◽  
pp. 10.1212/WNL.0000000000008364 ◽  
Author(s):  
Kim Wiegertjes ◽  
Annemieke ter Telgte ◽  
Pedro B. Oliveira ◽  
Esther M.C. van Leijsen ◽  
Mayra I. Bergkamp ◽  
...  

2011 ◽  
Vol 219 (1) ◽  
pp. 368-372 ◽  
Author(s):  
Elisa Cuadrado-Godia ◽  
Angel Ois ◽  
Eva Garcia-Ramallo ◽  
Eva Giralt ◽  
Sara Jimena ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ralph Klose ◽  
Alexander Prinz ◽  
Fabian Tetzlaff ◽  
Eva-Maria Weis ◽  
Iris Moll ◽  
...  

AbstractVascular smooth muscle cell (VSMC) dysfunction is a hallmark of small vessel disease, a common cause of stroke and dementia. Two of the most frequently mutated genes in familial small vessel disease are HTRA1 and NOTCH3. The protease HTRA1 cleaves the NOTCH3 ligand JAG1 implying a mechanistic link between HTRA1 and Notch signaling. Here we report that HTRA1 is essential for VSMC differentiation into the contractile phenotype. Mechanistically, loss of HTRA1 increased JAG1 protein levels and NOTCH3 signaling activity in VSMC. In addition, the loss of HTRA1 enhanced TGFβ-SMAD2/3 signaling activity. Activation of either NOTCH3 or TGFβ signaling resulted in increased transcription of the HES and HEY transcriptional repressors and promoted the contractile VSMC phenotype. However, their combined over-activation led to an additive accumulation of HES and HEY proteins, which repressed the expression of contractile VSMC marker genes. As a result, VSMC adopted an immature phenotype with impaired arterial vasoconstriction in Htra1-deficient mice. These data demonstrate an essential role of HTRA1 in vascular maturation and homeostasis by controlling Notch and TGFβ signaling.


2006 ◽  
Vol 354 (14) ◽  
pp. 1489-1496 ◽  
Author(s):  
Douglas B. Gould ◽  
F. Campbell Phalan ◽  
Saskia E. van Mil ◽  
John P. Sundberg ◽  
Katayoun Vahedi ◽  
...  

2017 ◽  
Vol 52 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Cezary Grochowski ◽  
Jakub Litak ◽  
Piotr Kamieniak ◽  
Ryszard Maciejewski

2016 ◽  
Vol 2 (11) ◽  
Author(s):  
C. Frances Fan ◽  
José R Romero

<p><span style="font-size: medium;">Stroke and dementia are the most common neurological disorders worldwide. Cerebrovascular disease, particularly cerebral small vessel disease (CSVD) is implicated in both, and the two main types of CSVD (hypertensive vasculopathy and cerebral amyloid angiopathy) account for the majority of cerebrovascular contributions to stroke and dementia. Current knowledge of CSVD may influence treatment decisions and preventive efforts. Although the causes of CSVD are not entirely elucidated, ongoing research of the pathophysiology of CSVD, such as the role of inflammation, is helping identify potential treatment targets, evaluate prediction models and develop preventive strategies. Given the detectability of CSVD in preclinical stages using brain MRI, a long window of opportunity is presented to implement existent preventive measures. This review considers CSVD including its subclinical manifestations detected using brain MRI, clinical manifestations, use of markers of CSVD as predictors of clinical outcomes such as dementia and stroke, and presents potential management strategies when seeing patients with cerebral small vessel disease to reduce its disease burden and clinical consequences.<span style="font-family: Calibri;"> C</span>linical trials have evaluated some aspects of CSVD treatment and are beginning to recognize CSVD as endpoint in subclinical stages. Future studies will clarify if this approach is able to delay onset of dementia and prevent stroke occurrence, meanwhile implementation of existent recommendations for the prevention and treatment of stroke and dementia may reduce disability and clinical outcomes related to CSVD. </span></p>


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