Know the potential biomarkers for the risk of cerebral aneurysms



It turns out that aneurysm occurs everywhere in the bloodstream, but usually develops along the aorta and in the blood vessels of the brain.

Expansive arterial remodeling (EAR) includes a genetically programmed biological response designed to restore homeostatic levels of arterial wall tension after an increase in blood flow load. The magnitude and speed of EAR responses to local hemodynamic stress fields and the tensile strength of vascular tissue determine whether the process will result in a stable mural structure (adaptive remodeling) or an unstable mural structure that proceeds to form an aneurysm (maladaptive remodeling) ).

A recent study revealed the molecular mechanisms that underlie adaptive and maladaptive remodeling of cerebral arteries for the first time.

In this study, the researchers streamed the basilar artery in rats by performing bilateral ligature of the carotid artery. Flow induced changes in basilar artery morphometry and histology were correlated with changes in mRNA expression and protein expression. These changes in the mural structure and biology were revealed by comparison of current loaded basilar arteries with basilar arteries from rats undergoing sham surgery. The adaptive and poorly adapted remodeling reactions were differentiated by comparing the results of an aneurysm-sensitive inbred strain of rats with an aneurysm-resistant inbred strain of rats.

The study revealed 24 genes that were differentially expressed between strains in the absence of current load (resting state). More than half of these genes are previously associated with pathological vascular phenotypes and more than a third have been specifically associated with aneurysmal pathology.

Numerous flow-induced genes were revealed by this study, including a group of 8 genes that displayed a very strong current-induced expression that was conserved in both inbred strains. A group of 9 genes showed a very strong flow-induced expression with large differences between an aneurysm-sensitive intimate rats and the aneurysm-resistant inbred rats. These genes are considered to play an important role in maladaptive cerebrovascular remodeling reactions that lead to mural stabilization and cerebral aneurysm formation. Three of these genes, including the Tgfb3, Ldha and Rgs16 genes, have been specifically associated with aneurysmal pathology in previous studies.

The newly discovered maladaptive cerebrovascular remodeling genes revealed by this study may allow the development of new diagnostic biomarker tests for patients at risk for cerebral aneurysm formation.

The products of maladaptive cerebrovascular remodeling genes may ultimately prove to be high-yielding drug targets for targeted arterial wall-stabilizing therapies. Such therapies may be particularly beneficial for individuals at high risk of aneurysm formation, including patients with severe hypertension, unilateral carotid artery incisions, cerebral arteriovenous malformations, and aneurysmal cerebral arteriopathies such as tuberous sclerosis, Alaglia syndrome, and sickle cell disease.

The findings published in the Journal of Current Neurovascular Research.

(This story is not edited by Business Standard staff and is automatically generated from a syndicated feed.)


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Know the potential biomarkers for the risk of cerebral aneurysms



It turns out that aneurysm occurs everywhere in the bloodstream, but usually develops along the aorta and in the blood vessels of the brain.

Expansive arterial remodeling (EAR) includes a genetically programmed biological response designed to restore homeostatic levels of arterial wall tension after an increase in blood flow load. The magnitude and speed of EAR responses to local hemodynamic stress fields and the tensile strength of vascular tissue determine whether the process will result in a stable mural structure (adaptive remodeling) or an unstable mural structure that proceeds to form an aneurysm (maladaptive remodeling) ).

A recent study revealed the molecular mechanisms that underlie adaptive and maladaptive remodeling of cerebral arteries for the first time.

In this study, the researchers streamed the basilar artery in rats by performing bilateral ligature of the carotid artery. Flow induced changes in basilar artery morphometry and histology were correlated with changes in mRNA expression and protein expression. These changes in the mural structure and biology were revealed by comparison of current loaded basilar arteries with basilar arteries from rats undergoing sham surgery. The adaptive and poorly adapted remodeling reactions were differentiated by comparing the results of an aneurysm-sensitive inbred strain of rats with an aneurysm-resistant inbred strain of rats.

The study revealed 24 genes that were differentially expressed between strains in the absence of current load (resting state). More than half of these genes are previously associated with pathological vascular phenotypes and more than a third have been specifically associated with aneurysmal pathology.

Numerous flow-induced genes were revealed by this study, including a group of 8 genes that displayed a very strong current-induced expression that was conserved in both inbred strains. A group of 9 genes showed a very strong flow-induced expression with large differences between an aneurysm-sensitive intimate rats and the aneurysm-resistant inbred rats. These genes are considered to play an important role in maladaptive cerebrovascular remodeling reactions that lead to mural stabilization and cerebral aneurysm formation. Three of these genes, including the Tgfb3, Ldha and Rgs16 genes, have been specifically associated with aneurysmal pathology in previous studies.

The newly discovered maladaptive cerebrovascular remodeling genes revealed by this study may allow the development of new diagnostic biomarker tests for patients at risk for cerebral aneurysm formation.

The products of maladaptive cerebrovascular remodeling genes may ultimately prove to be high-yielding drug targets for targeted arterial wall-stabilizing therapies. Such therapies may be particularly beneficial for individuals at high risk of aneurysm formation, including patients with severe hypertension, unilateral carotid artery incisions, cerebral arteriovenous malformations, and aneurysmal cerebral arteriopathies such as tuberous sclerosis, Alaglia syndrome, and sickle cell disease.

The findings published in the Journal of Current Neurovascular Research.

(This story is not edited by Business Standard staff and is automatically generated from a syndicated feed.)


Source link

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