**7. Endothelial dysfunction in stroke**

The global burden of neurological diseases including cerebrovascular stroke has significantly increased, and development of new treatment modalities for cerebrovascular diseases is an urgent need. Cerebrovascular stroke can be broadly subdivided into acute ischemic stroke and hemorrhagic stroke [66]. Acute ischemic stroke is among the leading causes of death and long-term disability. Cerebrovascular stroke in small vessel has functional (lacunar stroke, cognitive impairment, gait, and movement disorders) and structural (small subcortical infarct, lacunar infarct, lacunes, white matter lesions, and micro bleeds) consequences. In the past few decades, the immense development of neuro-radiological methods enabled better imaging of cerebral blood vessels. From the clinical point of view, it is very important to identify the location of vascular lesion. However,

the treatment strategies do not depend on the location of vascular impairment. It is now well recognized that endothelial dysfunction represents a systemic syndrome involving multiple vascular beds, including the cerebral vasculature [67]. Endothelial function is not uniform throughout the arterial system. It differs between organs and potentially also between different vascular beds within the same organ. Cerebral endothelium is probably one of the most specific types since it is the crucial element of the well-known blood-brain barrier (BBB). The BBB is a term used to describe the unique properties of the microvasculature of the central nervous system that protects the brain from harmful agents and pathogens [68]. CNS vessels are continuous non-fenestrated vessels, but also contain a series of additional properties that allow them to tightly regulate the movement of molecules, ions, and cells between the blood and the CNS. This heavily restricting barrier capacity allows BBB ECs to tightly regulate CNS homeostasis, which is critical to allow for proper neuronal function, as well as protect the CNS from toxins, pathogens, inflammation, injury, and disease. The cell-to-cell interaction with astrocytes, microglia, and neurons mainly played an important role for maintenance of BBB controlled by endothelial cells and pericytes [69].

However, the integrity of BBB is mainly disrupted due to decrease in endothelial cell-cell junction proteins and the detachment of pericytes from the endothelial membrane in homorganic condition [70]. Cerebral autoregulation maintains constant blood flow (CBF) through the brain in spite of changing mean arterial pressure. Autoregulation of cerebral blood flow consists of mechano- and chemoregulation. The serum level of carbon dioxide (CO2) is directly controlled by the chemo-regulation independent of changes in mean arterial pressure [71]. However, mechano-regulation depends on transmural pressure gradient and endothelial vasodilatation.

### **8. Conclusion**

From the above discussion, it is evident that CVDs and cardiovascular morbidity are associated with endothelial dysfunction, but the mechanistic links between inflammatory diseases, endothelial dysfunction, and CVDs have not been fully elucidated. The role of traditional cardiovascular risk factors in patients with inflammation, especially sterile inflammation, has received considerable attention, though traditional factors alone are insufficient to explain the excess burden of CVDs. It seems likely that sterile inflammation, a shared feature of CVDs, is involved in the pathogenesis of accelerated endothelial dysfunction.

Patients with chronic inflammatory/and or sterile inflammatory diseases are at high risk for cardiovascular morbidity and mortality. In many inflammatory diseases, this heightened risk of CVDs is reflected in early endothelial dysfunction, even in the absence of any other detectable diseases. Several others mechanisms, that is, auto-antibodies, oxidative stress, and interactions with traditional risk factors like dyslipidemia and insulin resistance might be involved. Therefore, further research in future is required to delineate the importance of these processes. So, the current approaches to diminish cardiovascular morbidity and mortality are focused on controlling traditional modifiable cardiovascular risk factors and reduction of disease risk. Therefore, the precise mechanisms leading to development of CVDs due to inflammation/or sterile inflammation need to explore. These studies might help to identify unique therapeutic targets to combat these diseases.

The endothelium therefore represents an integrator of vascular risk, and the study of its dysfunction may help elucidate mechanisms driving accelerated CVDs in future, which could help to develop therapeutic targets for control of CVDs.

**99**

**Author details**

Indranil Biswas1

Fiji Islands

and Gausal A. Khan2

\*Address all correspondence to: gausalk@gmail.com

Foundation, Oklahoma City, OK, USA

provided the original work is properly cited.

\*

1 Cardiovascular Biology Research Program, Oklahoma Medical Research

2 Department of Physiology, Fiji School of Medicine, Fiji National University, Suva,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Endothelial Dysfunction in Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.89365*

This work was supported by grant Grant Challenges Canada (R-ST-

**Acknowledgements**

POC-1807-13914) to GAK.

*Endothelial Dysfunction in Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.89365*
