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Biomedical subjects

H van Goor

Publications and source records attributed to H van Goor.

At least 19 recordsLinked to original sources
PubMed2007

Effect of combining ACE inhibition with aldosterone blockade on proteinuria and renal damage in experimental nephrosis.

Aldosterone has pro-fibrotic properties and is a potential target for additional intervention in patients with chronic renal disease showing resistance to therapy during treatment with angiotensin-converting enzyme inhibitors (ACEi). Combining ACEi and aldosterone receptor blockade (aldoRB) in proteinuric renal disease reduces proteinuria, but effects on proteinuria-induced renal damage are unknown. We studied the effect of ACEi/aldoRB in adriamycin nephrosis (AN). Six weeks after injection of adriamycin in Wistar rats, randomized treatment with vehicle (VEH, n=8), aldoRB (n=12), ACEi (n=10), or a combination of ACEi/aldoRB (n=14) was given for 12 weeks. Healthy rats served as controls (n=6). Renal damage was quantified by markers of tubular injury (osteopontin (OPN) and kidney injury molecule-1 (Kim-1)), pre-fibrotic lesions (alpha-smooth muscle actin (SMA)), interstitial fibrosis (IF), and focal glomerulosclerosis (FGS). In AN animals, proteinuria was increased compared with controls. ACEi and ACEi/aldoRB significantly reduced proteinuria compared with VEH, whereas aldoRB monotherapy was without effect. Blood pressure was reduced in ACEi and ACEi/aldoRB compared with VEH and aldoRB. OPN and Kim-1 were increased in AN animals, but significantly reduced by ACEi/aldoRB. Treatment with ACEi and ACEi/aldoRB prevented an increase of SMA, IF, and FGS. In conclusion, ACEi/aldoRB effectively reduced proteinuria and markers of tubular injury and prevented renal damage in this rat model of chronic proteinuria-induced renal damage.

Actins↗
PubMed2006

The omentum-polypropylene sandwich technique: an attractive method to repair large abdominal-wall defects in the presence of contamination or infection.

BACKGROUND: Repair of abdominal wall defects in the presence of contamination or infection continues to be a significant problem for surgeons. The loss of tissue warrants reinforcement of the abdominal wall, preferably by autologous material. However, autologous repair often requires extensive operations that carry a high morbidity. Moreover, the lack of sufficient fascia may be so extensive that insertion of a prosthetic material is inevitable. Polypropylene (PP) is the most appropriate material to use under these circumstances, but without coverage, the mesh will wrinkle and ultimately be extruded. The present report describes an alternative technique for repair of heavily contaminated abdominal-wall defects. PATIENTS: Two patients with a very large heavily contaminated abdominal wall defect due to necrotizing fasciitis in one patient and a lion's bite in the other were treated with the omental sandwich technique. After radical debridement, resulting in a full thickness loss of the abdominal wall, the peritoneum was restored using absorbable polyglactin mesh. The fascial defect was bridged with a PP mesh that was fixed to the adjacent myoaponeurosis and covered with a pedicled omental flap. In both patients the omentum was covered with a split skin. RESULTS: Wound healing in both patients was without complications. Both patients had a sufficient abdominal wall, without signs of herniation after a follow up of 4 and 30 months, respectively. CONCLUSION: The omental sandwich technique is an attractive method to repair large abdominal wall defects in the presence of contamination or overt infection.

Adult↗
PubMed2006

Antihypertensive therapy induces compartment-specific chemokine expression and a Th1 immune response in the clipped kidney of Goldblatt hypertensive rats.

The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure with increasing doses of a vasopeptidase inhibitor for 6 wk. The vasopeptidase inhibitor dose dependently lowered blood pressure. The tubulointerstitial damage was accompanied by a diffuse infiltration of mononuclear cells and circumscript mononuclear inflammatory cell cluster formation consisting mainly of T cells and to a lesser degree of macrophages and B cells. Real-time PCR analyses showed a dose-dependent induction of MCP-1 and the Th1-type chemokines IP10 and Mig as well as their receptor CXCR3 and the Th1 cytokine IFN-gamma. In situ hybridization and laser microdissection revealed a strong expression of these Th1-associated transcripts in the clusters and, in the case of MCP-1, also diffusely in the interstitium. The inflammation was accompanied by the appearance of myofibroblasts and synthesis of the fibrogenic factor plasminogen activator inhibitor-1 as well as the collagenase matrix metalloproteinase-2, leading to collagen I upregulation and interstitial scarring. No inflammation or fibrosis was found in normotensive rats treated with the vasopeptidase inhibitor. The renal injury in the clipped kidney is accompanied by compartment-specific chemokine expression and cell cluster formation of Th1 specificity associated with upregulation of fibrogenic proteins and matrix metalloproteinases. These findings suggest that the Th1 chemokines IP10 and Mig as well as their receptor CXCR3 are potential targets for therapeutic interventions in ischemic nephropathy.

Actins↗
PubMed2006

ADAM19 expression in human nephrogenesis and renal disease: associations with clinical and structural deterioration.

ADAM19, an enzyme from the ADAM (a disintegrin and metalloproteinase) family, is involved in various cell-cell and cell-matrix interactions. It can cleave epidermal growth factor (EGF)-like growth factors, such as heparin-binding (HB)-EGF and neuregulin (NRG), from the cell membrane. ADAM-mediated EGF receptor activation is crucial in the development of renal pathology. Based on these data, we studied ADAM19 in human nephrogenesis and renal disease. We collected 20 fetal kidneys and 56 biopsies from patients with various renal diseases. The unaffected part of kidneys from eight patients with renal cell carcinoma served as control. RNA in situ hybridization revealed widespread ADAM19 mRNA expression in the nephrogenic zone of human fetal kidneys. Normal human kidneys showed constitutive ADAM19 expression in distal tubules and endothelial cells, whereas proximal tubules were negative. In renal disease, ADAM19 was de novo expressed in proximal tubules and glomerular mesangium and upregulated in distal tubules and endothelial cells. ADAM19 colocalized with tubular and interstitial NRG, however, not with HB-EGF. Independent of renal disorder, mesangial ADAM19 expression was associated with glomerular damage as assessed by mesangial matrix expansion, focal glomerulosclerosis, and glomerular macrophage influx (all P<0.001). ADAM19 in proximal tubules and in peritubular capillaries was associated with interstitial fibrosis (P<0.05). Finally, increasing tubular ADAM19 was associated with declining renal function (P<0.05). The abundant ADAM19 expression during nephrogenesis points to a role in growth promotion and regulation. The high ADAM19 expression in renal disease suggests involvement in profibrotic and proinflammatory processes leading to renal deterioration.

ADAM Proteins↗
PubMed2006

Effect of thoracoscopic splanchnic denervation on pain processing in chronic pancreatitis patients.

BACKGROUND: Central sensitisation due to visceral pancreatic nociceptive input may play an important role in chronic pancreatitis pain. Using quantitative sensory testing (QST), this first study investigates whether thoracoscopic splanchnic denervation (TSD), performed to reduce nociceptive visceral input, affects central sensitisation in chronic pancreatitis patients. PATIENTS AND METHODS: We studied 19 chronic pancreatitis patients (11 men, 8 women on stable opioid medication) and 18 healthy volunteers as preoperative controls. Preoperatively and 6 weeks after TSD, pain numeric rating scores, opioid medication, and thresholds to electric skin stimulation and pressure pain (measured in dermatomes T10 (pancreas), C5, T4, L1, L4) were documented. Treatment success was defined as cessation of opioids 6 weeks after TSD. RESULTS: Six weeks after TSD, there was a trend towards lower pain scores, only 10 patients were still on opioids (P<0.05 vs. preoperatively) and thresholds overall were significantly higher than preoperatively (pressure pain: +25%, P<0.001; electric: sensation +55%, pain detection +34%, pain tolerance +21%, P<0.05). Gender-specific differences in hypoalgesia patterns were seen. Preoperatively, TSD treatment successes consumed significantly less opioids than failures, without significant differences in preoperative patterns of neuroplasticity. CONCLUSIONS: TSD for chronic pancreatitis pain resulted in fewer patients on opioids and overall increases in pain thresholds. Our results suggest that TSD for reducing visceral nociceptive input may be effective in reducing resulting central sensitisation. Although patients benefiting from TSD consume less opioids preoperatively, we were unable to clearly link treatment success with specific perioperative patterns of neuroplasticity such as the presence or absence of hyperalgesia.

Adult↗
PubMed2006

Pharmacological management of pain in chronic pancreatitis.

Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.

Animals↗
PubMed2006

Guideline proposal to reconstructive surgery for complex perineal sinus or rectal fistula.

AIM: To evaluate a guideline approach of reconstructive surgery for complex perineal sinus or rectal fistula. METHODS: pre-, per-, and postoperative data of 28 patients undergoing transposition of rectus abdominis muscle (TRAM), gracilis muscle (GM), gluteal thigh flap (GTF), or omentoplasty (OP) for complex perineal sinus or rectal fistula were analyzed. A fistula higher than 10 cm and a sinus with a length of >10 cm were treated with TRAM or OP. If <8 cm, the first choice was GM or GTF. The operative team made choice between 8 and 10 cm. Vacuum assisted closure (VAC) therapy was used as adjunct therapy before and after muscle transposition in huge sinus. Success was defined as no residual or recurrent sinus or fistula within 6 months, postoperatively. Long-term complaints of perineum and muscle donor site were assessed. RESULTS: Twenty-five out of 28 patients (90%) were treated according to the guideline. VAC therapy was done in six. Three patients died during mean follow up of 40 months (6-90). Initial success rate was 61% (17/28). After secondary surgery in seven, four (57%) were successful. Overall success rate, including VAC therapy, was 79% (22/28). Success was highest with GM and GTF and in small sinus or fistula. CONCLUSION: A guideline approach to complex perineal sinus or fistula based on length or height of the sinus or rectal fistula, respectively, is successful in about 80% of cases. Large defects may best be downsized by VAC therapy, followed by muscle flap. Long-term complaints are acceptable.

Abscess↗
PubMed2006

Adhesion formation and reherniation differ between meshes used for abdominal wall reconstruction.

Incisional hernia is a common surgical problem, frequently requiring prosthetic mesh repair. The demands of the ideal mesh seem conflicting; ingrowth at the mesh-fascia interface, without development of adhesions at the visceral mesh surface. Various antiadhesives combined with macroporous mesh and composite meshes were studied for prevention of adhesions to mesh and ingrowth into the fascia. In 60 rats an abdominal wall defect was created and repaired with underlay mesh. Rats were divided into six groups and treated with polypropylene mesh (PPM, control), PPM with auto-cross-linked polymers (ACP) gel, PPM with fibrinogen glue (FG), polypropylene/expanded polytetrafluoroethylene (ePTFE) mesh, polypropylene/sodium hyaluronate/carboxymethylcellulose (HA/CMC) mesh, and polypropylene-collagen/polyethylene-glycol/glycerol (CPGG) mesh. Mesh infection was assessed in the postoperative period, adhesions and reherniations were scored at sacrifice 2 months after operation, and tensile strength of the mesh-tissue interface was measured. Six rats developed mesh infection, half of them were treated with PPM/ePTFE. The PPM/HA/CMC group showed a significant reduction in the amount and severity of adhesions. In animals treated with PPM/ACP and PPM/FG, severity of adhesions was reduced as well. Reherniation rate in the PPM/ACP group was 50% and significantly higher than that in other groups. Rats in the PPM/HA/CMC had the highest tensile strength. PPM/HA/CMC approaches the demands of the ideal mesh best, having superior antiadhesive properties, no reherniation and no infection in this rat model of incisional hernia.

Abdominal Wall↗
PubMed2006

Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period.

BACKGROUND: Selective cyclo-oxygenase 2 (COX-2) inhibitors are increasingly prescribed in the perioperative period. Recent recognition of a possible role for COX-2 in wound healing has raised concerns about the safety of their use in surgical practice. Therefore, the influence of celecoxib, a selective COX-2 inhibitor, on early anastomotic healing was investigated. METHODS: Celecoxib, in doses of 15, 50 or 200 mg per kg per day, was given daily from the day before operation onwards to male Wistar rats that received both ileal and colonic anastomoses. Anastomotic strength was assessed by measuring the breaking strength and bursting pressure on the third day after operation. A second group received a dose of 50 mg per kg per day and a colonic anastomosis only, and healing was assessed on the third and fifth day after surgery. RESULTS: Expression of COX-2 protein was upregulated in the anastomotic area. Administration of celecoxib, at all doses tested, resulted in a significantly higher ileal dehiscence rate than in control rats (P = 0.002). In contrast, colonic anastomoses healed normally within the same animals. The latter was confirmed in rats with colonic anastomoses only. CONCLUSION: In this model, administration of the COX-2 inhibitor celecoxib affected ileal but not colonic anastomotic healing in the early postoperative period.

Anastomosis, Surgical↗
PubMed2006

Decreased levels of mucosal detoxification enzymes in the pouch of patients with familial adenomatous polyposis.

BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus 4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.

Adenomatous Polyposis Coli↗
PubMed2006

ACE inhibition has adverse renal effects during dietary sodium restriction in proteinuric and healthy rats.

Angiotensin-converting enzyme inhibitors (ACEi) provide renoprotection. A low sodium diet enhances their efficacy. However, the added effect of sodium restriction on proteinuria and blood pressure is not invariably associated with better preservation of renal morphology, suggesting that the combination of ACEi with a low sodium diet can elicit renal structural abnormalities. To test this hypothesis, the effects of ACEi in combination with a control (CS) or a low sodium (LS) diet were investigated in healthy rats and in adriamycin nephrotic rats. After 3 weeks of treatment, rats were sacrificed and kidneys examined for renal structural abnormalities. In healthy rats, ACEi reduced blood pressure: the fall in blood pressure was significantly greater in the ACEi/LS group. Renal morphology was normal in the ACEi/CS group but severe interstitial damage was found in the ACEi/LS group. This was associated with increased interstitial macrophage influx and up-regulation of osteopontin, alpha-smooth muscle actin, and collagen III expression. In addition, ACEi/LS induced an increase in the total medial area of afferent arterioles. In nephrotic rats, ACEi/LS reduced both blood pressure and proteinuria, whereas only blood pressure was reduced in the ACEi/CS group. Mild interstitial damage was present in the ACEi/CS group but, strikingly, pronounced tubulo-interstitial abnormalities occurred in the ACEi/LS group, similar to those seen in ACEi/LS healthy rats, with similar changes in afferent arteriolar walls. In conclusion, the combination of ACEi/LS elicits pronounced renal interstitial abnormalities in healthy and nephrotic rats, despite a significant reduction of proteinuria in the latter. Considering their occurrence in healthy rats, these renal adverse effects cannot be due to specific characteristics of adriamycin nephrosis. Further studies should elucidate the mechanisms underlying these observations and their impact on long-term renoprotection.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Diagnosis and treatment of acute appendicitis in children: a survey among Dutch surgeons and comparison with evidence-based practice.

BACKGROUND: Considerable variability exists in the surgical approach to acute appendicitis in children, affecting both quality and costs of care. A national survey provides insight into daily surgical practice and enables comparison of practice with the available evidence. METHODS: A national survey was conducted in all 121 Dutch hospitals asking detailed information concerning diagnosis and treatment of children suspected of acute appendicitis. An evidence-based practice (EBP) score was developed on the basis of a critical appraisal of the literature, allowing for classification of reported practices with regard to the level of evidence and identification of hospitals working in accordance with the best available evidence. RESULTS: The overall response rate was 93%. For the diagnosis of acute appendicitis, respondents relied predominantly on patient history (29%) and clinical examination (31%), followed by laboratory results (22%). Only 20% of the departments routinely measured total white blood cell count (WBC), C-reactive protein (CRP) and leukocyte differential count (proportion of polymorphonuclear cells), being part of the triad that provides diagnostic evidence. Although strong evidence exists in favour of routine prophylaxis for suspected appendicitis, only two thirds of surgical departments reported this as part of their routine practice. For a number of issues, reasonably consistent evidence is available (e.g. primarily versus delayed closure, drainage versus lavage, routine peritoneal culturing). Thirty-eight percent of the departments routinely cultured abdominal fluid despite various reports that it provides no therapeutic advantage. Not more than 22% of the departments closed the skin in perforated appendicitis in spite of clear supportive evidence. Considerable variation exists in cleaning the abdomen in perforated appendicitis, despite evidence favouring lavage. Comparing departments in terms of compliance with available evidence revealed that most paediatric surgery departments worked according to evidence-based medicine. CONCLUSIONS: Available evidence on diagnosis and treatment of acute appendicitis in children is only partly applied in a small proportion of hospitals in the Netherlands. It is recommended that national guidelines be published, which could decrease health care costs and increase more uniform policy, improve quality of care for this group of patients and improve training of residents in general surgery in the Netherlands.

Acute Disease↗
PubMed2006

Enhanced transduction of fibroblasts in transplanted kidney with an adenovirus having an RGD motif in the HI loop.

Application of gene therapy to the renal graft has a powerful potential to improve the outcome of kidney transplantation and eliminate detrimental side effects associated with systemic therapy, through local expression of immunoregulatory or other protective molecules. However, the search for the optimal vector is still ongoing. In this study, we used a modified adenovirus that has an Arg-Gly-Asp (RGD) motif inserted in the HI loop of the fiber knob, as a successful strategy to transduce the renal graft. Donor Lewis rat kidneys were infused via the renal artery with a solution containing either a fiber-modified adenovirus (AdTL-RGD) or an unmodified adenovirus (AdTL), or with saline. Syngeneic recipients were killed after 3, 7 or 14 days. Efficiency, selectivity, localization, time course of gene expression and side effects were studied using biochemical and immunohistological techniques. Enhanced gene expression was achieved selectively in the transplanted kidney by AdTL-RGD, when compared to AdTL. Transgene expression lasted for at least 2 weeks. With the AdTL-RGD vector, the transgene was abundantly expressed in the renal interstitial fibroblasts. An increase in the number of cytotoxic T lymphocytes accompanied the use of either vector, when compared to saline. These data convincingly show enhanced and selective gene transfer to the fibroblasts of transplanted kidneys using an RGD-modified adenovirus, providing a highly efficient vector system for future therapeutic interventions.

Adenoviridae↗
PubMed2006

Upregulation of ADAM19 in chronic allograft nephropathy.

ADAM19 (a disintegrin and metalloproteinase 19) is involved in cell-cell and cell-matrix interactions and tumor necrosis factor (TNF)-alpha shedding. We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys. Reverse transcriptase (RT) PCR revealed an upregulation of ADAM19 mRNA in CAN when compared with control kidneys (p = 0.002). Using RNA in situ hybridization (ISH), we detected moderate ADAM19 mRNA expression in vascular smooth muscle cells (SMCs) and distal tubuli of control kidneys. In CAN, massive ADAM19 expression was detected in SMCs, distal tubuli, glomerular sclerotic lesions and inflammatory CD4+ cells. To determine whether ADAM19 is specifically related to CAN, we studied transplant biopsies with and without CAN, acute rejection and non-transplant-related kidney diseases: interstitial fibrosis (IF), interstitial atrophy, glomerular fibrosis and interstitial inflammation. In various renal structures, ADAM19 mRNA was significantly higher in CAN when compared with renal allografts without CAN or acute rejection. ADAM19 expression in renal endothelium was significantly higher in acute rejection when compared with renal allografts without CAN. When compared to CAN, ADAM19 was expressed to a similar extent in non-transplant-related interstitial and glomerular fibrosis, interstitial atrophy and inflammation. Although these observational data do not establish a cause and effect relationship, ADAM19 may have a modulatory role in the dysfunctional renal allograft state.

ADAM Proteins↗
PubMed2005

No detrimental effects of repeated laparotomies on early healing of experimental intestinal anastomoses.

BACKGROUND: Little is known about the impact of repeated laparotomies on intestinal anastomotic healing. While experimental data are completely lacking, the sparse data available from clinical studies report high anastomotic failure rates, suggesting a negative effect in this respect. Since the unequivocal determination of such an effect may have important consequences for choosing the optimal treatment strategy for patients suffering from intra-abdominal infection, an experimental study has been performed in an established rodent model. METHODS: Intestinal anastomoses were constructed in healthy Wistar rats (ileal and colonic anastomoses) or 24 h after peritonitis was induced by caecal ligation and puncture (colonic anastomosis only). Rats were then scheduled to undergo no, one (after 24 h) or two relaparotomies (after 24 and 48 h). Anastomotic strength was assessed 3 and 5 days after anastomotic construction. On the third post-operative day anastomotic hydroxyproline levels, matrix metalloproteinase activity and myeloperoxidase activity were measured. RESULTS: No negative impact of repeated laparotomies was measured on any of the parameters measured. Under non-infectious conditions even an improvement in breaking strength (+48%, p=0.017) but not bursting pressure was found after two relaparotomies, but only in the ileum on the third post-operative day. CONCLUSIONS: In this experimental setting, early anastomotic healing is not adversely affected by repeated laparotomies.

Anastomosis, Surgical↗
PubMed2004

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.

Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations.

Arteries↗
PubMed2004

Renal ACE2 expression in human kidney disease.

Angiotensin-converting enzyme 2 (ACE2) is a recently discovered homologue of angiotensin-converting enzyme (ACE) that is thought to counterbalance ACE. ACE2 cleaves angiotensin I and angiotensin II into the inactive angiotensin 1-9, and the vasodilator and anti-proliferative angiotensin 1-7, respectively. ACE2 is known to be present in human kidney, but no data on renal disease are available to date. Renal biopsies from 58 patients with diverse primary and secondary renal diseases were studied (hypertensive nephropathy n = 5, IgA glomerulopathy n = 8, minimal change nephropathy n = 7, diabetic nephropathy n = 8, focal glomerulosclerosis n = 5, vasculitis n = 7, and membranous glomerulopathy n = 18) in addition to 17 renal transplants and 18 samples from normal renal tissue. Immunohistochemical staining for ACE2 was scored semi-quantitatively. In control kidneys, ACE2 was present in tubular and glomerular epithelium and in vascular smooth muscle cells and the endothelium of interlobular arteries. In all primary and secondary renal diseases, and renal transplants, neo-expression of ACE2 was found in glomerular and peritubular capillary endothelium. There were no differences between the various renal disorders, or between acute and chronic rejection and control transplants. ACE inhibitor treatment did not alter ACE2 expression. In primary and secondary renal disease, and in transplanted kidneys, neo-expression of ACE2 occurs in glomerular and peritubular capillary endothelium. Further studies should elucidate the possible protective mechanisms involved in the de novo expression of ACE2 in renal disease.

Angiotensin-Converting Enzyme 2↗