Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction.

Paul, Martin; Wagner, Juergen; Dzau, V J

doi:10.1172/jci116428

Cited by 227 publications

(80 citation statements)

References 31 publications

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“…In addition, components of RAS could also be produced in some tissues (local RAS or tissue RAS), such as adipose tissue, brain, heart and so on. [11][12][13][14] Furthermore, Ang II can also be generated by enzymes of the nonrenin-angiotensin system, such as cathepsin D and cathepsin G. [15][16][17][18] So far, it is generally believed that Ang II is derived from AGT, irrespective of which way is chosen for its formation.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

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Objective: The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures. Methods: Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation. Results: Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation. Conclusions: Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application.

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Section: Introductionmentioning

confidence: 99%

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

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“…Several studies have demonstrated that ANG I [13] and ANG II [39] are present in the placenta and the uteroplacental unit possesses all components of the RAS necessary for their generation [12]; renin [14], angiotensin [40] and ACE [15]. However, the impact of the altered RAS on the fetal side of the placenta is not well defined [41,42].…”

Section: Discussionmentioning

confidence: 99%

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

2007

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Inadequate blood flow and increased vasoconstriction of the placenta contribute to pregnancy associated disorders such as preeclampsia (PE). Because placental vessels lack autonomic innervation, humoral effects of the placenta must play critical roles in regulation of fetal-placental vascular contractility. In this study, we examined the nature of humoral factors produced by PE trophoblasts on placental vessel contractility using an organ bath perfusion model. Vasomotor responses were studied in vitro using placental chorionic plate arteries. Vessel rings from third branch chorionic plate arteries were dissected from human placentas following normal or PE delivery. The arterial rings were equilibrated in Krebs Henseleit buffer and exposed to placental conditioned medium, which was prepared by culture of villous tissue from PE placentas. Receptor antagonists for angiotensin II (ANG II), thromboxane (TX), and endothelin (ET) were used to determine which humoral factor produced by placental tissue (trophoblasts) was more effective in promoting vasoconstriction. The role of angiotensin converting enzyme (ACE) and non-ACE ANG II generating enzymes in regulation of placental vasomotor tone were also investigated. A total of 80 arterial rings from 48 placentas were studied. Our results showed: 1) enhanced vasomotor tone in arteries from PE placentas compared to those from normal placentas; 2) PE-CM induced vaso-constrictive activity could be partially attenuated by receptor antagonists for TX, ANG II and ET, respectively; and 3) chymostatin (a chymase inhibitor) produced a stronger inhibitory effect than captopril (ACE inhibitor) on PE conditioned medium induced vasoconstriction. Our data demonstrate increased vasocontractility in PE placentas and suggest that the non-ACE pathway is probably a major source of ANG II produced in the human placenta.

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“…M Angiotensin release from isolated vessels 16 and the presence of renin mRNA 17 in the blood vessel wall have been demonstrated in human tissue. However, the bulk of direct evidence for vascular angiotensin production has been derived from studies in rats.…”

Section: Discussionmentioning

confidence: 99%

Vascular renin in the guinea pig. Suppression by the renin inhibitor remikiren.

et al. 1994

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Angiotensin I and II are generated by the vascular wall. Whether this generation depends on renin or on other enzymes is debated. We tested the hypothesis that remikiren, a highly specific inhibitor of human and guinea pig renin, may inhibit the vascular renin-angiotensin system. Isolated hindquarters from guinea pigs were perfused with an artificial medium, and angiotensin I and II release was measured by high-performance liquid chromatography and radioimmunoassay. Guinea pig hindquarters released angiotensin I (23.8±5.6 fmol/30 min; n = 13) and angiotensin II (95.2±19 fmol/30 min; n=13) spontaneously. Inhibition of the angiotensin I-convert-T he notion that angiotensin I and angiotensin II (Ang I and Ang II, respectively) are formed in and released from extrarenal resistance vessels is now supported by numerous data from studies in isolated perfused organs. '-4 However, nonrenin enzymes could contribute to the local formation of Ang I 5 ' 6 in isolated organs perfused without blood, ie, in the absence of plasma-derived protease inhibitors. We have recently shown that the natural renin substrate angiotensinogen is cleaved in an isolated, perfused resistance vessel bed.3 These data provide indirect evidence for the presence of renin in resistance vessels, since other enzymes would not form Ang I from angiotensinogen at pH greater than 7. 6 To demonstrate the presence of vascular renin directly, inhibition of vascular angiotensin formation by specific renin inhibitors is necessary. Saito et al 2 have shown that vascular angiotensin formation in rat mesentery can be suppressed by a derivative of pepstatin that inhibits rat renin. However, concentrations of pepstatin that inhibit rat renin also inhibit nonspecific proteases such as cathepsin D. 6More specific inhibitors for rat renin are not available.Remikiren (RO 42-5892) is a highly specific renin inhibitor in primates that is 3500 times more potent against renin than against cathepsin D.7 Furthermore, several in vivo studies suggest that remikiren inhibits renin at tissue sites, eg, vascular renin. -8 Therefore, remikiren appears to be well suited to investigate vascular renin. Remikiren is not active against rat renin but is a highly specific inhibitor of guinea pig renin. To test the hypothesis that remikiren inhibits vascular renin, we adapted our rat hindquarter perfusion mod- ing enzyme by captopril (10 nmol/mL) suppressed angiotensin II by 85% and increased angiotensin I by 352% (n=5, P<.05). Infusion of remikiren (1.6 nmol/mL) in addition to captopril decreased angiotensin I release by 68% (P<.05 versus captopril alone, n=5 each). We conclude that renin generates angiotensin I in an isolated guinea pig resistance vessel bed. Our study demonstrates that renin rather than nonrenin enzymes is responsible for the major part of vascular angiotensin formation. 1 -3 for guinea pigs. We investigated whether perfused guinea pig hindquarters release Ang I and Ang II and tested the effects of Ang I-converting enzyme (ACE) inhibition and remikiren. The ren...

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Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction.

Cited by 227 publications

References 31 publications

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

Vascular renin in the guinea pig. Suppression by the renin inhibitor remikiren.

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