scholarly journals Vaginal dryness in primary Sjögren’s syndrome: a histopathological case–control study

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2806-2815 ◽  
Author(s):  
Jolien F van Nimwegen ◽  
Karin van der Tuuk ◽  
Silvia C Liefers ◽  
Gwenny M Verstappen ◽  
Annie Visser ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Dysfunction ◽  
Muscle Cells ◽  
Lymphocytic Infiltration ◽  
Immune Markers ◽  
Vaginal Dryness ◽  
Vaginal Health ◽  
Oncogene Homologue ◽  
Cervicovaginal Lavage

Abstract Objective The aim was to study clinical, histopathological and immunological changes in the vagina and cervix of women with primary SS, which might explain vaginal dryness. Methods We included 10 pre-menopausal female primary SS patients with vaginal dryness and 10 pre-menopausal controls undergoing a laparoscopic procedure. The vaginal health index was recorded. Multiplex immunoassays and flow cytometry were performed on endocervical swab and cervicovaginal lavage samples to evaluate cellular and soluble immune markers. Mid-vaginal and endocervical biopsies were taken and stained for various leucocyte markers, caldesmon (smooth muscle cells), avian V-ets erythroblastosis virus E26 oncogene homologue (ERG; endothelial cells) and anti-podoplanin (lymphatic endothelium). The number of positive pixels per square micrometre was calculated. Results One patient was excluded because of Clamydia trachomatis, and two controls were excluded because of endometriosis observed during their laparoscopy. Vaginal health was impaired in primary SS. CD45+ cells were increased in vaginal biopsies of women with primary SS compared with controls. Infiltrates were predominantly located in the peri-epithelial region, and mostly consisted of CD3+ lymphocytes. In the endocervix, CD45+ infiltrates were present in patients and in controls, but a higher number of B lymphocytes was seen in primary SS. Vascular smooth muscle cells were decreased in the vagina of primary SS patients. No differences were found in leucocyte subsets in the vaginal and endocervical lumen. CXCL10 was increased in endocervical swab samples of primary SS patients. Conclusion Women with primary SS show impaired vaginal health and increased lymphocytic infiltration in the vagina compared with controls. Vaginal dryness in primary SS might be caused by vascular dysfunction, possibly induced by IFN-mediated pathways.

Abstract 34: Diminished Contractile Capability In Cerebral Vascular Smooth Muscle Cells In The TgF344-AD Rat Model Of Alzheimer's Disease

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Xing Fang ◽  
Huawei Zhang ◽  
Yedan Liu ◽  
Shaoxun Wang ◽  
Baoying Zheng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Rat Model ◽  
Perfusion Pressure ◽  
Vascular Dysfunction ◽  
Muscle Cells ◽  
Model Of Alzheimer’S Disease ◽  
Cerebral Vascular

We recently reported that cerebral vascular dysfunction leads to impaired autoregulation of cerebral blood flow (CBF), neurovascular coupling (NVC), and blood-brain barrier (BBB) leakage. The present study examined if cerebral vascular dysfunction precedes cognitive impairment in the TgF344-AD (AD) rat model of Alzheimer's disease. In the present study, we confirmed that the AD rats develop learning and memory deficits beginning at 24-week of age using an eight-arm water maze. AD rats (n = 11) took a longer time to escape and displayed more errors than age-matched wildtype (WT) rats (n = 6). We also completed a longitudinal comparison of the myogenic response (MR) of the middle cerebral artery (MCA) and found that the MR was similar in AD and WT rats at 8- to 12-week of age when perfusion pressure was increased from 40 to 180 mmHg. However, the MR was significantly reduced in 16-week old AD rats (n = 6) as the inner diameter of the MCA only decreased by 8.2 ± 2.4% when perfusion pressure was increased from 40 to 180 mmHg compared with 14.5% ± 2.0% in age-matched WT rats (n = 6). The impaired MR of the MCA was exacerbated in AD rats with aging. Autoregulation of CBF AD rats (n = 4) in vivo was impaired in the surface and deep cortex at 24-week of age compared to age-matched WT rats (n = 4). Furthermore, we found the contractile capability of the cerebral vascular smooth muscle cells (VSMCs) isolated from AD rats (n = 4) was significantly reduced compared with WT rats (n = 4), detected by the reduction in size of 15.7 ± 0.9% vs. 25.4 ± 1.0% using a collagen gel-based assay kit. These results provide evidence that cerebral VSMC dysfunction, impaired MR, and autoregulation of CBF precede the development of memory and learning deficits in the TgF344-AD rat model. However, the underlying mechanisms for the loss of VSMCs contractility in this AD model overexpressing mutant human amyloid precursor protein ( APPsw ) and presenilin 1 ( PS1ΔE9 ) genes remain to be determined. Nevertheless, these results provide novel insight into the vascular contribution to AD.

Abstract 209: Resistin Regulates Dynamin-Related Protein 1, a Mitochondrial Fission Protein in Vascular Smooth Muscle Cells

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Takara A Scott ◽  
Sharon Francis
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Dysfunction ◽  
Mitochondrial Fission ◽  
Muscle Cells ◽  
Related Protein ◽  
Mitochondrial Fragmentation ◽  
Over Expression

Recent studies indicate increased mitochondrial fission and organ dysfunction in models of obesity. While the mechanisms for this morphological alteration are not completely understood it is likely that the altered adipokine profile that occurs during obesity may play a permissive role in enhanced mitochondrial fragmentation. In this study, we investigated the role of resistin, a pro-inflammatory adipokine that is elevated in the plasma of obese individuals, on regulation of the mitochondrial fission protein, dynamin-related protein 1(DNM1L) in vascular smooth muscle cells (VSMCs). We hypothesized that serum and glucocorticoid inducible kinase 1 (SGK1) plays a role in resistin-induced mitochondrial fission expression in VSMCs. In dose and time response studies, we found that resistin stimulated DNM1L protein levels in both rat and human aortic smooth muscle cells suggesting a role for resistin in regulation of mitochondrial fission. In addition, we observed that resistin enhances expression and activity of SGK1. To determine whether SGK1 regulates resistin-mediated expression of DNM1L, we examined the effect of SGK1 over-expression, or inhibition on resistin-induced expression of DNM1L. Over-expression of wildtype SGK1 potentiated resistin-mediated DNM1L expression, while dominant-negative SGK1 inhibited resistin-mediated expression of DNM1L in human VSMC. In conclusion, we have demonstrated for the first time that SGK1 is a potential downstream mediator of resistin. Interestingly, SGK1 activity has been linked to pathological vascular remodeling in various cardiovascular disease settings. Our data suggests that the elevated plasma levels of resistin that occur in obese individuals may lead to activation of SGK1. This in turn, could exacerbate mitochondrial fragmentation in VSMC and predispose to the development of vascular dysfunction that is evident during obesity. Together with further mitochondrial fission studies, additional elucidation of how resistin also alters components of mitochondrial fusion machinery may uncover novel mechanisms of potential theraputic targets for obesity-mediated vascular dysfunction.

scholarly journals 181 Nox compartmentalization and protein oxidation in vascular smooth muscle cells – implications in vascular dysfunction in hypertension

Heart ◽  
2017 ◽  
Vol 103 (Suppl 5) ◽  
pp. A125.1-A125
Author(s):  
Livia de Lucca Camargo ◽  
Augusto Cesar Montezano ◽  
Sofia Tsiropoulou ◽  
Adam Harvey ◽  
Katie Hood ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Protein Oxidation ◽  
Vascular Dysfunction ◽  
Muscle Cells

Abstract 060: Mitochondrial Deacetylase Sirt3 in Endothelial and Smooth Muscle Cells Protects From Vascular Dysfunction and Attenuates Hypertension

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Anna Dikalova ◽  
Arvind Pandey ◽  
Liang Xiao ◽  
Hana Itani ◽  
Tatiana Sidorova ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Dysfunction ◽  
Muscle Cells

scholarly journals TMEM16A channel upregulation in arterial smooth muscle cells produces vasoconstriction during diabetes

2021 ◽  
Author(s):  
M. Dennis Leo ◽  
Dieniffer Peixoto-Neves ◽  
Wen Yin ◽  
Somasundaram Raghavan ◽  
Padmapriya Muralidharan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Current Density ◽  
Vascular Dysfunction ◽  
Muscle Cells ◽  
Cell Types ◽  
Myogenic Tone ◽  
Arterial Smooth Muscle ◽  
Functional Consequences ◽  
Arterial Smooth Muscle Cells

The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium-activated chloride (Cl-) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arterial smooth muscle cells and total and surface TMEM16A protein in resistance-size cerebral and hindlimb arteries of mice. To examine vascular cell types in which TMEM16A protein increased and the functional consequences of TMEM16A upregulation during T2D, we generated tamoxifen-inducible, smooth muscle-specific TMEM16A knockout (TMEM16A smKO) mice. T2D increased both TMEM16A protein and Cl- current density in arterial smooth muscle cells of control (TMEM16Afl/fl) mice. In contrast, T2D did not alter arterial TMEM16A protein or Cl- current density in smooth muscle cells of TMEM16A smKO mice. Intravascular pressure stimulated greater vasoconstriction (myogenic tone) in arteries of T2D TMEM16Afl/fl mice than in arteries of non-diabetic TMEM16Afl/fl mice. This elevation in myogenic tone in response to T2D was abolished in arteries of T2D TMEM16A smKO mice. T2D also reduced Akt2 protein and activity in arteries of T2D mice. siRNA-mediated knockdown of Akt2, but not Akt1, increased arterial TMEM16A protein in non-diabetic mice. In summary, data indicate that T2D is associated with an increase in TMEM16A expression and currents in arterial smooth muscle cells that produces vasoconstriction. Data also suggest that a reduction in Akt2 function drives these pathological alterations during T2D.

Involvement of transforming growth factor-β in regulation of calcium transients in diabetic vascular smooth muscle cells

2003 ◽  
Vol 285 (6) ◽  
pp. F1258-F1270 ◽  
Author(s):  
Kumar Sharma ◽  
Leo Deelman ◽  
Muniswamy Madesh ◽  
Bernd Kurz ◽  
Emilio Ciccone ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Transforming Growth Factor ◽  
Vascular Dysfunction ◽  
Muscle Cells ◽  
Diabetic Rats ◽  
Calcium Transients ◽  
Ang Ii

Altered calcium [Ca2+] transients of vascular smooth muscle cells to vasoconstrictors may contribute to altered regulation of blood flow in diabetes. We postulated that diabetes-induced transforming growth factor (TGF)-β production contributes to impaired ANG II response of vascular smooth muscle cells in macrovessels and microvessels. Aortic vascular smooth muscle cells isolated from diabetic rats exhibited markedly impaired ANG II-induced cytosolic calcium [Ca2+] signal that was completely restored by pretreatment with anti-TGF-β antibodies. Similar findings were noted in microvascular smooth muscle cells isolated from preglomerular vessels and cultured in high glucose. The impact of diabetes on [Ca2+] transients was replicated by addition of TGF-β1 and -β2 isoforms to aortic smooth muscle cells in culture and diabetic cells had enhanced production of TGF-β2. In the in vivo condition, TGF-β1 was increased in diabetic glomeruli, whereas TGF-β2 was increased in diabetic aorta. The characteristic increase in glomerular filtration surface area found in diabetic rats was prevented by treatment with anti-TGF-β antibodies, and impaired ANG II-induced aortic ring contraction in diabetic rats was completely restored by anti-TGF-β antibodies. Impaired vascular dysfunction may be partly due to decreased inositol 1,4,5-trisphosphate receptor (IP3R), as reduced type I IP3R expression was found in diabetic aorta and restored by anti-TGF-β antibodies. We conclude that TGF-β plays an important role in the vascular dysfunction of early diabetes by inhibiting calcium transients in vascular smooth muscle cells.

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