Angiogenic imbalance and diminished matrix metalloproteinase-2 and -9 underlie regional decreases in uteroplacental vascularization and feto-placental growth in hypertensive pregnancy

Dias‐Junior, Carlos A.; Chen, Juanjuan; Cui, Ning; Chiang, Charles L.; Zhu, Minglin; Ren, Zongli; Possomato-Vieira, José Sérgio; Khalil, Raouf A.

doi:10.1016/j.bcp.2017.09.005

Cited by 20 publications

(26 citation statements)

References 95 publications

(173 reference statements)

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“…We did not observe any differences in the number of viable fetuses among groups; however, fetal weight was decreased in hypertensive animals. Fetal growth restriction is a common feature of hypertension‐in‐pregnancy . We confirmed that hypertensive pregnancy caused a decrease in fetal weight while the treatment with NaHS improved fetal weight in HTN‐Preg+NaHS animals.…”

Section: Discussionsupporting

confidence: 74%

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Possomato-Vieira

Chimini

Silva

et al. 2018

Clin Exp Pharma Physio

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Dysregulation of hydrogen sulphide (H S) producing enzymes has been related to hypertensive pregnancy, and H S donor, sodium hydrosulphide (NaHS) exerts antihypertensive effects, modulates angiogenic factors production and acts as an antioxidant. Moreover, reduction in nitric oxide (NO) bioavailability is related to hypertensive pregnancy and H S may interact with NO, modulating its production. We aimed to investigate the NaHS effects in hypertension-in-pregnancy and also in feto-placental parameters. Female Wistar rats (200-250 g) were mated and desoxycorticosterone acetate injections followed by replacement of water by 0.9% saline solution were used to induce hypertensive pregnancy. Rats were divided into four groups: normal pregnant (Norm-Preg), pregnant + NaHS (Preg+NaHS), hypertensive pregnant (HTN-Preg) and HTN-Preg+NaHS. Systolic blood pressure was increased in HTN-Preg and this increase was blunted in HTN-Preg+NaHS. Fetal and placental weights were decreased in HTN-Preg animals, while fetal growth restriction was improved in HTN-Preg+NaHS. Placental weight was lower in HTN-Preg+NaHS than in HTN-Preg; however, placental efficiency was re-established in HTN-Preg+NaHS rats. We observed that a partial contribution of placental NO, but not changes in anti-angiogenic factors may mediate the increases in placental efficiency in HTN-Preg+NaHS. HTN-Preg presented thoracic aorta hyperreactivity to phenylephrine while NaHS treatment blunted this hyperreactivity, which seems not to be related to NO-mediated relaxation induced by acetylcholine. Therefore, changes in vascular responsiveness promoted by NaHS treatment may underlie the beneficial effects in systolic blood pressure and feto-placental parameters in our study.

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Section: Discussionsupporting

confidence: 74%

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Possomato-Vieira

Chimini

Silva

et al. 2018

Clin Exp Pharma Physio

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“…Furthermore, vascular remodeling disorders of the uterine and placenta hypoperfusion have been generally recognized in prior years [ 61 ]. A number of studies have evaluated the key role of matrix metalloproteinase-2 and -9 in healthy [ 62 , 63 , 64 , 65 ] and complicated pregnancies [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ].…”

Section: Impaired Types I and Iv Collagen Turnover In Preeclampsiamentioning

confidence: 99%

“…They concluded that localized angiogenic imbalance and decreased MMP-2 and MMP-9 could cause further decline in placental and myoendometrial vascularization and placental and fetal growth in distal as compared with proximal uterus of HTN-Preg rats, in addition to a general reduction in placental and fetal growth during uteroplacental ischemia. Of note, regional differences in uteroplacental perfusion, angiogenic balance, and MMPs could be a factor in the incidence of preeclampsia in multiple pregnancy [ 70 ].…”

Section: Impaired Types I and Iv Collagen Turnover In Preeclampsiamentioning

confidence: 99%

“…Previous studies have described the measurement of matrix metalloproteinase-2 in samples of experimental animal model involving RUPP rats with hypertensive disorders of pregnancy vs. normal pregnant rats. The data showed decreased levels/activity of MMP-2 [ 66 , 67 , 68 , 69 , 70 ]. Contrary to that, human studies of women with HDP report increased MMP-2 levels/activity [ 49 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Limitations and Future Prospectus On The Application Of Mmentioning

confidence: 99%

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Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers

Николов

Popovski

2021

Diagnostics

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Gelatinases (matrix metalloproteinase-2 and -9) are enzymes from the matrix metalloproteinases (MMPs) family, which are associated with collagen degradation. MMP-2 is capable of cleaving gelatine, types I and IV collagens, while MMP-9 is incapable of direct proteolysis of collagen I and digests collagen type IV. MMP-2 and -9 are both important regulators of vascular and uterine remodeling in a healthy pregnancy. Alterations in the collagen structure of the uterus and spiral arteries are observed in women with hypertensive disorders of pregnancy. Dysregulation of MMP-2 and MMP-9 has been implicated in abnormal vasodilation, placentation, and uterine expansion in preeclampsia. Early preeclampsia detection is paramount for risk stratification and prevention of further complications. Understanding the role of MMP-2 and-9 in uteroplacental and vascular remodeling could help design new approaches for prediction and management of preeclampsia. This review presents a general survey of MMP-2 and MMP-9 faulty regulation and impaired collagen types I and IV turnover in complicated pregnancies. Their potential role as circulating markers for diagnosis, prognosis, and monitoring of preeclampsia development is discussed as well.

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“…30 From the middle of pregnancy, the circulating level of sFlt-1 in preeclampsia patients is significantly higher than that in normal pregnant women. 31 The noncanonical Wnt5a signaling pathway can control vascular formation in the retina in mice, possibly by changing the splicing pattern of VEGFR1 to produce sFlt-1, which acts as a negative regulator of angiogenesis to suppress angiogenesis. 10…”

Section: Discussionmentioning

confidence: 99%

Construction of a vascularized bladder with autologous adipose-derived stromal vascular fraction cells combined with bladder acellular matrix via tissue engineering

et al. 2019

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The formation of an effective vascular network can promote peripheral angiogenesis, ensuring an effective supply of blood, oxygen, and nutrients to an engineered bladder, which is important for bladder tissue engineering. Stromal vascular fraction cells (SVFs) promote vascularization and improve the function of injured tissues. In this study, adipose tissue-derived SVFs were introduced as an angiogenic cell source and seeded into the bladder acellular matrix (BAM) to generate a SVF-BAM complex for bladder reconstruction. The morphological regeneration and functional restoration of the engineered bladder were evaluated. In addition, we also explored the role of the Wnt5a/sFlt-1 noncanonical Wnt signaling pathway in regulating the angiogenesis of SVFs, and in maintaining the rational capability of SVFs to differentiate into vasculature in regenerated tissues. Histological assessment indicated that the SVF-BAM complex was more effective in promoting smooth muscle, vascular, and nerve regeneration than BAM alone and subsequently led to the restoration of bladder volume and bladder compliance. Moreover, exogenous Wnt5a was able to enhance angiogenesis by increasing the activity of MMP2, MMP9, and VEGFR2. Simultaneously, the expression of sFlt-1 was also increased, which enhanced the stability of the SVFs angiogenic capability. SVFs may be a potential cell source for tissue-engineered bladders. The Wnt5a/sFlt-1 pathway is involved in the regulation of autologous vascular formation by SVFs. The rational regulation of this pathway can promote neo-microvascularization in tissue-engineered bladders.

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Angiogenic imbalance and diminished matrix metalloproteinase-2 and -9 underlie regional decreases in uteroplacental vascularization and feto-placental growth in hypertensive pregnancy

Cited by 20 publications

References 95 publications

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers

Construction of a vascularized bladder with autologous adipose-derived stromal vascular fraction cells combined with bladder acellular matrix via tissue engineering

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