Oxyhemoglobin-Induced Expression of R-Type Ca
            <sup>2+</sup>
            Channels in Cerebral Arteries

Link, Timothy E.; Murakami, Kentaro; Beem-Miller, Micah; Tranmer, Bruce I.; Wellman, George C.

doi:10.1161/strokeaha.107.508754

Cited by 33 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, Timothy E, et al . demonstrated that the hemoglobin contributes to excessive cerebral artery constriction following SAH18. After the incubation of hemoglobin with VSMC to mimic neuropathology of SAH, our results firstly revealed that hemoglobin pretreatment could also lead to cerebral VSMC phenotypic switch, causing dramatic downregulation of contractile proteins and overexpression of synthetic proteins in VSMC, consistent with the animal observation following SAH.…”

Section: Discussionsupporting

confidence: 79%

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

Zhang

Jiang

Guo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARβ/δ in VSMC phenotypic switch following SAH. Activation of PPARβ/δ by GW0742 and adenoviruses PPARβ/δ (Ad-PPARβ/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPARβ/δ on VSMC phenotypic switch were partly obstacled in the presence of LY294002, a potent inhibitor of Phosphatidyl-Inositol-3 Kinase-AKT (PI3K/AKT). Furthermore, following study demonstrated that PPARβ/δ-induced PI3K/AKT activation can also contribute to Serum Response Factor (SRF) nucleus localization and Myocardin expression, which was highly associated with VSMC phenotypic switch. Finally, we found that Ad-PPARβ/δ positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPARβ/δ by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia.

show abstract

Section: Discussionsupporting

confidence: 79%

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

Zhang

Jiang

Guo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Despite expression of Ca V 2.1 across species, functional differences in channel function are evident: ω-agatoxin dose-dependently inhibits K + -induced constriction in human but not murine intrarenal arteries (552). In cerebral arteries expression and function of R-type VGCCs (Ca V 2.3) appears after exposure to oxyhemoglobin as occurs during hemorrhagic stroke, contributing to the vasospasm that often occurs after this type of cerebrovascular accident (879). …”

Section: Voltage-gated Ca2+ Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

283

347

View full text Add to dashboard Cite

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

show abstract

“…Several authors suggest that the functional significance of R-type channels may lie within small diameter blood vessels and that blood vessels of different sizes are impacted differently by SAH [58]. Furthermore, exposure of organ cultured rabbit cerebral arteries to oxyHb induces the expression of R-type VGCC mRNA in small vessels rendering the vessels sensitive to SNX-482 (R-type antagonist) and less sensitive to diltiazem [59]. SNX-482 was also found to attenuate CBF reduction after SAH in rats [60].…”

Section: Changes In Ion Channel Expression and Function In Delayedmentioning

confidence: 99%

Calcium and Potassium Channels in Experimental Subarachnoid Hemorrhage and Transient Global Ischemia

Kamp

Dibué

Schneider

et al. 2012

Stroke Research and Treatment

View full text Add to dashboard Cite

Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each other. Initial hypoperfusion after exposure of cerebral vessels to oxyhemoglobin correlates with a suppression of voltage-gated potassium channel activity, whereas delayed cerebral vasospasm involves changes in other potassium channel and voltage-gated calcium channels expression and function. Furthermore, expression patterns and function of ion channels appear to differ between main and small peripheral vessels, which may be key in understanding mechanisms behind subarachnoid hemorrhage-induced vasospasm. Here, changes in calcium and potassium channel expression and function in animal models of subarachnoid hemorrhage and transient global ischemia are systematically reviewed and their clinical significance discussed.

show abstract

Oxyhemoglobin-Induced Expression of R-Type Ca ²⁺ Channels in Cerebral Arteries

Cited by 33 publications

References 36 publications

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Calcium and Potassium Channels in Experimental Subarachnoid Hemorrhage and Transient Global Ischemia

Contact Info

Product

Resources

About

Oxyhemoglobin-Induced Expression of R-Type Ca 2+ Channels in Cerebral Arteries

Cited by 33 publications

References 36 publications

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Calcium and Potassium Channels in Experimental Subarachnoid Hemorrhage and Transient Global Ischemia

Contact Info

Product

Resources

About

Oxyhemoglobin-Induced Expression of R-Type Ca ²⁺ Channels in Cerebral Arteries