Differential effects of statins on endogenous H2S formation in perivascular adipose tissue

Wójcicka, Grażyna; Jamróz-Wiśniewska, Anna; Atanasova, Pepa; Chaldakov, George N.; Chylińska-Kula, Beata; Bełtowski, Jerzy

doi:10.1016/j.phrs.2010.10.011

Cited by 92 publications

(77 citation statements)

References 44 publications

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“…40 Interestingly, vasoconstrictors as well as the statin atorvastatin seem to increase the release of H 2 S from the PVAT in rats, thus increasing its anticontractile effect. 41,42 Importantly, NaHS, a H 2 S donor, can cause a dose-dependent relaxation that is inhibited by treatment with the KCNQ (K v 7) channel blocker XE991. 40 The cystathionine-γ-lyase inhibitor β-cyano-l-alanine had no effect on coronary flow, which might be explained by organ differences or low-dose β-cyano-l-alanine used in this study.…”

Section: Pvrf: Potential Candidatesmentioning

confidence: 99%

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Tano

Schleifenbaum

Gollasch

2014

ATVB

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Abstract-Perivascular adipose tissue has been recognized unequivocally as a major player in the pathology of metabolic and cardiovascular diseases. Through its production of adipokines and the release of other thus far unidentified factors, this recently discovered adipose tissue modulates vascular regulation and the myogenic response. After the discovery of its ability to diminish the vessel's response to vasoconstrictors, a new paradigm established adipose-derived relaxing factor (ADRF) as a paracrine smooth muscle cells' potassium channel opener that could potentially help combat vascular dysfunction. This review will discuss the role of ADRF in vascular dysfunction in obesity and hypertension, the different potassium channels that can be activated by this factor, and describes new pharmacological tools that can mimic the ADRF effect and thus can be beneficial against vascular dysfunction in cardiovascular disease. [19][20][21][22] and are also observable on veins. 23 The release of ADRF from PVAT is strongly dependent on the concentration of Ca 2+ and seems to be dependent on the activation of intracellular pathways involving tyrosine kinase and protein kinase A. In contrast, perivascular nerve endings, notably presynaptic neuronal N-type Ca 2+ , Na + channels, calcitonin gene-related peptide, cannabinoid, and vanilloid receptors, do not play an important role in this process.4 Importantly, recent experiments have shown a dual role of PVAT in the initiation and progression of obesity. In effect, PVAT (similarly to endothelium) in animal and human models of hypertension, obesity, and metabolic syndrome becomes dysfunctional and loses its anticontractile properties, likely because of a decrease in PVRF release. 16,[24][25][26][27] It is, therefore, of utmost importance to determine the nature of PVRFs as well as its targets for the paracrine regulation of PVAT. PVRF: Potential CandidatesSeveral studies have tried to pinpoint the nature of PVRFs. The role of adiponectin as PVRF has been thus far inconclusive. Vessels from the aorta and mesenteric arteries of adiponectin-knockout mice have been initially shown to maintain their anticontractile properties. 16 In contrast, recent studies in mesenteric vessels of wild-type mice advance that the vasorelaxing and hyperpolarizing effects of adiponectin rely on the opening of maxi Ca 2+ -activated K + (BK Ca ) channels. 28,29 In addition, a factor that might be adiponectin is released after stimulation of rat and murine mesenteric arteries with β3 adrenoreceptor. This latter factor seems to exert its paracrine effect by activation of AMPK and opening of BK ca channels. 30 Similarly to adiponectin, leptin has also been proposed as a candidate for PVRF in a hypertension mouse model. 31 Leptin, however, is perhaps not ADRF in the systemic circulation because the PVAT of Zucker fa/fa rats that lack the leptin receptor still display anticontractile properties. 3 As mentioned above, angiotensin-1 to 7 and methyl palmitate are also proposed as PVRF. A study using aortas from...

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Section: Pvrf: Potential Candidatesmentioning

confidence: 99%

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Tano

Schleifenbaum

Gollasch

2014

ATVB

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“…This plus the fact that the capacity of cells to oxidize sulfide appears to be considerably greater than the estimated rate of sulfide production (24) ensures that intracellular H 2 S concentrations are very low. Interestingly, the statin, atorvastatin, increases H 2 S production in perivascular adipose tissue by producing coenzyme Q 9 deficiency and thereby inhibiting mitochondrial oxidation (189).…”

Section: Metabolism (Inactivation)mentioning

confidence: 99%

The therapeutic potential of hydrogen sulfide: separating hype from hope

Olson

2011

American Journal of Physiology-Regulatory, Integrative and Comp

163

154

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Hydrogen sulfide (H2S) has become the hot new signaling molecule that seemingly affects all organ systems and biological processes in which it has been investigated. It has also been shown to have both proinflammatory and anti-inflammatory actions and proapoptotic and anti-apoptotic effects and has even been reported to induce a hypometabolic state (suspended animation) in a few vertebrates. The exuberance over potential clinical applications of natural and synthetic H2S-“donating” compounds is understandable and a number of these function-targeted drugs have been developed and show clinical promise. However, the concentration of H2S in tissues and blood, as well as the intrinsic factors that affect these levels, has not been resolved, and it is imperative to address these points to distinguish between the physiological, pharmacological, and toxicological effects of this molecule. This review will provide an overview of H2S metabolism, a summary of many of its reported “physiological” actions, and it will discuss the recent development of a number of H2S-donating drugs that show clinical potential. It will also examine some of the misconceptions of H2S chemistry that have appeared in the literature and attempt to realign the definition of “physiological” H2S concentrations upon which much of this exuberance has been established.

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“…Atorvastatin could play important role by increasing net H 2 S production in PVAT (Wojcicka et al, 2011;Beltowski and Jamroz-Wisniewska, 2012).…”

Section: Pharmacotherapeutic Targetsmentioning

confidence: 99%