Evaluation of a new skin closure device in surgical incisions associated with breast procedures.

BACKGROUND: A novel topical skin adhesive system was developed to close the outermost layer of skin in an expeditious manner. To determine its clinical utility in breast procedures, a prospective clinical investigation was undertaken to demonstrate equivalence of a new adhesive (PRINEO™ Skin Closure System) to intradermal sutures in wound closure. METHODS: The investigation comprised 79 patients who underwent elective surgery for bilateral breast procedures. Each breast incision was randomized to wound closure with the PRINEO™ Skin Closure System or intradermal sutures (used in accordance with standard local practice). Postoperative evaluations took place at 24 hours, 7 days, 12-25 days, 90 days, 6 months, and 12 months. Data were collected on the continuous approximation of the skin edges, the time required to close the include final skin layer, the evaluation of incision healing, and cosmesis outcomes. Safety evaluations were related to the incidence and extent of local acute inflammatory reactions, clinical infection, skin blistering, and adverse events. RESULTS: PRINEO™ Skin Closure System was found to be equivalent to intradermal sutures for the continuous approximation of wounds associated with breast procedures. The upper limit of the one-sided 95% confidence interval for difference in proportions was less than the predetermined 12%, at 5.9%. The mean time to closure for the PRINEO™ Skin Closure System was 2.56 minutes, which was 13.66 minutes faster than that for intradermal sutures (16.22 minutes, P < 0.0001). Time savings may be less if 2 operators close simultaneously. On the other hand, because the device can be applied by 1 operator, the assistant's time may be freed up to attend to other tasks. Both treatments had similar incision healing and cosmetic outcomes. No quantitative or qualitative differences of clinical significance were evident between the treatment groups for local acute inflammatory reactions, clinical infection, or skin blistering. The number of serious adverse events was low, although the number of adverse events was higher, with 54/79 patients experiencing at least 1 adverse event. CONCLUSION: PRINEO™ Skin Closure System can be considered equivalent to intradermal sutures for full-thickness surgical incisions associated with breast procedures, with regard to safety and effectiveness. It was also 6.3 times faster than intradermal sutures for wound closure.

Promotion of incisional wound repair by human mesenchymal stem cell transplantation.

The purpose of this study was to determine the effect of transplanted human mesenchymal stem cells (hMSCs) on wound healing. In this model, full-thickness cutaneous wounds were created by incision in the skin of adult New Zealand white rabbits and treated by transplanted hMSCs into the wounds. Wound healing was evaluated by histological analysis and tensiometry over time. A total of 15 New Zealand white rabbits with 10 wounds per animal were examined in this study. Animals were treated with hMSCs and euthanised at 3, 7, 14, 21 and 80 days after manipulation. The hMSCs were labelled with a fluorescent dye (CM-DiI), suspended in phosphate-buffered saline and used to treat full-thickness incisional wounds in rabbit skin. Tensiometry and histology were used to characterise the wound-healing rate of the incisional wounds. These results showed that transplanted hMSCs significantly inhibited scar formation and increased the tensile strength of the wounds. Importantly, MSCs from genetically unrelated donors did not appear to induce an immunologic response. In conclusion, human mesenchymal stem cell therapy is a viable approach to significantly affect the course of normal cutaneous wound healing and significantly increase the tensile strength.

Dealing with the mass: a new approach to facilitate panniculectomy in patients with very large abdominal aprons.

BACKGROUND: Panniculectomy surgery is performed to remove a massive pannus, or abdominal apron, which frequently contributes to a number of health concerns. The resection of such a massive abdominal panniculus is technically difficult due to the weight of the tissue and the difficulty in handling it during surgery. METHODS: We performed a retrospective review on 20 morbidly obese patients (14 male, six female) who underwent a panniculectomy with a resection weight of >6 kg between November 2003 and November 2007 at our department. RESULTS: The patients' weight ranged from 90 to 240 kg, with a mean weight of 157.6 kg. The redundant pannus weighed from 6.8 to 60.0 kg. Uncomplicated healing occurred in 55% of cases. Further complications were not observed. CONCLUSIONS: The treatment of a massive panniculus requires a multitask management considering optimal conditions for the surgeon and patient. Based on our experience from 20 patients over 4 years, we are able to present our standardized and improved technique using a mechanical lift and a tumescent solution to facilitate this procedure.

Effect of adenoviral mediated overexpression of fibromodulin on human dermal fibroblasts and scar formation in full-thickness incisional wounds.

Fibromodulin, a member of the small leucine-rich proteoglycan family, has been recently suggested as a biologically significant mediator of fetal scarless repair. To assess the role of fibromodulin in the tissue remodeling, we constructed an adenoviral vector expressing human fibromodulin cDNA. We evaluated the effect of adenovirus-mediated overexpression of fibromodulin in vitro on transforming growth factors and metalloproteinases in fibroblasts and in vivo on full-thickness incisional wounds in a rabbit model. In vitro, we found that Ad-Fibromodulin induced a decrease of expression of TGF-beta(1) and TGF-beta(2) precursor proteins, but an increase in expression of TGF-beta(3) precursor protein and TGF-beta type II receptor. In addition, fibromodulin overexpression resulted in decreased MMP-1 and MMP-3 protein secretion but increased MMP-2, TIMP-1, and TIMP-2 secretion, whereas MMP-9 and MMP-13 were not influenced by fibromodulin overexpression. In vivo evaluation by histopathology and tensile strength demonstrated that Ad-Fibromodulin administration could ameliorate wound healing in incisional wounds. In conclusion, although the mechanism of scar formation in adult wounds remains incompletely understood, we found that fibromodulin overexpression improves wound healing in vivo, suggesting that fibromodulin may be a key mediator in reduced scarring.

Preclinical evaluation of transcriptional targeting strategies for carcinoma of the breast in a tissue slice model system.

INTRODUCTION: In view of the limited success of available treatment modalities for metastatic breast cancer, alternative and complementary strategies need to be developed. Adenoviral vector mediated strategies for breast cancer gene therapy and virotherapy are a promising novel therapeutic platform for the treatment of breast cancer. However, the promiscuous tropism of adenoviruses (Ads) is a major concern. Employing tissue specific promoters (TSPs) to restrict transgene expression or viral replication is an effective way to increase specificity towards tumor tissues and to reduce adverse effects in non-target tissues such as the liver. In this regard, candidate breast cancer TSPs include promoters of the genes for the epithelial glycoprotein 2 (EGP-2), cyclooxygenase-2 (Cox-2), alpha-chemokine SDF-1 receptor (stromal-cell-derived factor, CXCR4), secretory leukoprotease inhibitor (SLPI) and survivin. METHODS: We employed E1-deleted Ads that express the reporter gene luciferase under the control of the promoters of interest. We evaluated this class of vectors in various established breast cancer cell lines, primary breast cancer cells and finally in the most stringent preclinical available substrate system, constituted by precision cut tissue slices of human breast cancer and liver. RESULTS: Overall, the CXCR4 promoter exhibited the highest luciferase activity in breast cancer cell lines, primary breast cancer cells and breast cancer tissue slices. Importantly, the CXCR4 promoter displayed a very low activity in human primary fibroblasts and human liver tissue slices. Interestingly, gene expression profiles correlated with the promoter activities both in breast cancer cell lines and primary breast cancer cells. CONCLUSION: These data suggest that the CXCR4 promoter has an ideal 'breast cancer-on/liver-off' profile, and could, therefore, be a powerful tool in Ad vector based gene therapy or virotherapy of the carcinoma of the breast.

Gene transfer to carcinoma of the breast with fiber-modified adenoviral vectors in a tissue slice model system.

Successful adenoviral (Ad) vector-mediated strategies for breast cancer gene therapy and virotherapy have heretofore been hindered by low transduction efficiency. This has recently been understood to result from a relative paucity of expression of the primary adenovirus receptor, coxsackie-adenovirus-receptor (CAR), on primary tumor cells. To further investigate this issue, we evaluated the expression of CAR on breast cancer cell lines as well as primary breast cancer cells. With the exception of one patient sample, CAR expression was notably higher in the tumor cells from patients compared to CAR expression in the tumor cell lines. Furthermore, we explored CAR-independent targeting strategies to breast cancer tissue by exploring a panel of infectivity-enhanced Ad vectors, which contain CAR-independent targeting motifs for their utility in breast cancer gene therapy and virotherapy. These targeting motifs included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7), and were tested using the breast cancer tissue slice model, which is the most stringent substrate system available. Of all the tested tropism modified Ad vectors, Ad5/3 exhibited the highest transductional efficiency in breast cancer. These preclinical results suggest that Ad5/3 is the most useful modification to achieve higher clinical efficacy of breast cancer gene therapy and virotherapy.

Circumferential body contouring: the lower body lift.

A 2-position circumferential approach for body contouring of the lower trunk is presented. Mostly indicated in patients after massive weight loss, this approach allows the simultaneous skin resection and reshaping in the abdominal, flank, lateral thigh, back, and gluteal region in the same operation, with only one position change during surgery. Reconstruction of the abdominal wall and gluteal restoration allow volume and shape enhancement with autologous tissue transpositioning. This article explains the required preconditions, assessment of gluteal deformities, and perioperative management of this procedure, and presents common complications.

Central pedicled breast reduction technique in male patients after massive weight loss.

Male patients after massive weight loss often suffer from redundant skin and soft tissue in the anterior and lateral chest region, causing various deformities of pseudogynecomastia. Techniques with free or pedicled nipple-areola complex (NAC) transposition are widely accepted. The authors present their approach to male breast reduction with preservation of the NAC on a central dermoglandular pedicle and a wide elliptical tissue excision of breast and lateral thorax tissue in combination with liposuction. Male breast reduction was performed on patients after moderate to massive weight loss due to diet or bariatric procedures. Former procedures included free nipple-areola grafts or inferior pedicled techniques for NAC preservation. As a modification, we performed a central pedicled breast reduction on nine male patients with excessive liposuction of the pedicle and a horizontal elliptical skin removal, allowing for sufficient tissue removal at the lateral thorax. From October 2010 until June 2011, nine male patients had central pedicled breast reconstructions after massive weight loss. Mean age was 29.1 years, mean preoperative body mass index was 29.2, and mean preoperative weight loss was 63.9 kg. The chest wall improvement was rated "very good" by eight patients. No major complications occurred in all nine patients. Male chest deformities after massive weight loss can be dealt by several approaches. The optimal scar positioning and the preservation of NAC may be the most challenging aspects of these procedures. Therefore, the preservation of the NAC on a central dermoglandular pedicle with a horizontal submammary scar course may optimize the esthetic outcome.

A comparison of a new skin closure device and intradermal sutures in the closure of full-thickness surgical incisions.

BACKGROUND: A novel topical skin adhesive system was developed to close the outermost layer of skin in an expeditious manner. To determine its clinical utility, a clinical investigation was undertaken to demonstrate equivalence of a new adhesive skin closure system (Prineo Skin Closure System) to intradermal sutures in wound closure. METHODS: The investigation included 83 patients who underwent elective abdominoplasty, circumferential body lift procedures, and breast reconstruction with deep inferior epigastric perforator flaps. Incisions were divided in half, and each half was randomized to wound closure with the new skin closure system, including a pressure-sensitive adhesive mesh tape for wound edge approximation and next-generation cyanoacrylate or intradermal sutures. Postoperative evaluations took place at 24 hours, 7 days, 12 to 25 days, 90 days, 6 months, and 12 months. RESULTS: The new skin closure system was found to be equivalent to intradermal sutures for the continuous approximation of wounds. The upper limit of the two-sided 90 percent confidence interval for difference in proportions was 10.9 percent. The mean time to closure for the new skin closure system was 1.46 minutes, approximately 5 minutes faster than that for intradermal sutures (p < 0.0001). Both treatments had similar incision healing and cosmetic outcomes. No quantitative or qualitative differences of clinical significance were evident between the treatment groups. CONCLUSIONS: The Prineo Skin Closure System can be considered equivalent to intradermal sutures for full-thickness surgical incisions with regard to safety and effectiveness. The ease and speed of application contribute to shortened operative times (4.5 times faster than intradermal sutures).

The scarpa lift--a novel technique for minimal invasive medial thigh lifts.

Abdominoplasty and lower body lift procedures are the most common and sufficient procedures to correct abdominal tissue redundancy. Frequently, patients who undergo these procedures have lost a relevant amount of weight and additionally present tissue redundancy in the area of the medial thighs. Patients with mild to moderate skin surplus in the medial thigh region often refuse an additional scar in this specific region. For these cases, the medial thigh region can be indirectly treated by the vertical scarpa lift, sparing the medial thigh approach and consequent complications such as scar descent or vulvar distortion. Additionally, the lymphatic vessels below the scarpa fascia can be preserved, reducing the postoperative abdominal seroma rate.

Circumferential lower truncal dermatolipectomy.

Obesity and overweight in the general population have increased significantly over the last several years. Such increases have stimulated many approaches to treat this condition from a clinical perspective, with improved surgical and conservative measures that have become available for controlling overweight. The present article examines both established procedures for performing body lift procedures and innovative approaches that are now available, as well as their potential complications. The problems and solutions discussed in this article derive from the authors' own experiences collected over the last 10 years at the Department of Plastic and Reconstructive Surgery at the Dreifaltigkeits-Hospital in Wesseling, Germany. These surgical procedures are the operations with the largest treated body surface area with manageable risks when the planning and operation are performed meticulously and conscientiously.

Cancer-specific targeting of a conditionally replicative adenovirus using mRNA translational control.

BACKGROUND: In view of the limited success of available treatment modalities for a wide array of cancer, alternative and complementary therapeutic strategies need to be developed. Virotherapy employing conditionally replicative adenoviruses (CRAds) represents a promising targeted intervention relevant to a wide array of neoplastic diseases. Critical to the realization of an acceptable therapeutic index using virotherapy in clinical trials is the achievement of oncolytic replication in tumor cells, while avoiding non-specific replication in normal tissues. In this report, we exploited cancer-specific control of mRNA translation initiation in order to achieve enhanced replicative specificity of CRAd virotherapy agents. Heretofore, the achievement of replicative specificity of CRAd agents has been accomplished either by viral genome deletions or incorporation of tumor selective promoters. In contrast, control of mRNA translation has not been exploited for the design of tumor specific replicating viruses to date. We show herein, the utility of a novel approach that combines both transcriptional and translational regulation strategies for the key goal of replicative specificity. METHODS: We describe the construction of a CRAd with cancer specific gene transcriptional control using the CXCR4 gene promoter (TSP) and cancer specific mRNA translational control using a 5'-untranslated region (5'-UTR) element from the FGF-2 (Fibroblast Growth Factor-2) mRNA. RESULTS: Both in vitro and in vivo studies demonstrated that our CRAd agent retains anti-tumor potency. Importantly, assessment of replicative specificity using stringent tumor and non-tumor tissue slice systems demonstrated significant improvement in tumor selectivity. CONCLUSIONS: Our study addresses a conceptually new paradigm: dual targeting of transgene expression to cancer cells using both transcriptional and mRNA translational control. Our novel approach addresses the key issue of replicative specificity and can potentially be generalized to a wide array of tumor types, whereby tumor selective patterns of gene expression and mRNA translational control can be exploited.

Transpalpebral decompression of endocrine ophthalmopathy by intraorbital fat removal (Olivari technique): experience and progression after more than 3000 operations over 20 years.

BACKGROUND: Graves' ophthalmopathy is a chronic, multisystem disorder characterized by increased intraorbital fat tissue and hypertrophic extraocular muscles caused by an autoimmune process. Graves' ophthalmopathy represents the most frequent extrathyroidal manifestation of Graves' disease. Clinical findings are impaired ocular motility, diplopia, lid retraction, and impaired visual acuity up to optic neuropathy, with menacing blindness. METHODS: Transpalpebral decompression by intraorbital fat removal was first described by Olivari in 1988. From 1984 to 2004, a consecutive series of 1635 patients (3210 eyes) with Graves' ophthalmopathy underwent this operation at the authors' institution. The medical records of 1374 patients (84 percent) could be evaluated retrospectively. RESULTS: Postoperatively, the majority of patients showed significant improvements of major symptoms such as ocular protrusion, diplopia, decreased visual acuity, swelling of the eyelids, retrobulbar pressure, and headache. In addition, complications-most of them temporary and reversible-were rare. Because the osseous orbita is not touched, no complications, such as penetration of the dura, infection of the sinus maxillaris, meningitis, irritation of the infraorbital nerve, or obstruction of the lacrimal system, were observed. However, the high number of additional eyelid corrections (average, 2.5 individual corrections) following the decompression indicated the complexity of surgical treatment in endocrine orbitopathy. CONCLUSION: Transpalpebral decompression has proved to be reliable, effective, and safe, with good, lasting results leading to an improvement not only in visual function but also in the patient's personal well-being and social life, with a high-benefit-to-low-risk ratio.

Polymethylmethacrylate for managing frontal bone deformities.

The correction of bony frontal deformities has been accomplished with a variety of autogenous and alloplastic materials. Of the various materials currently available, polymethylmethacrylate (PMMA), a valuable biomaterial, has proved to be effective in reconstructing deformities of the frontal bone. The authors present one case of acquired frontal bone deformity reconstructed by subperiostal application of PMMA through a minimally invasive coronal approach. Our preliminary experience with this method has been promising.

Combining high selectivity of replication via CXCR4 promoter with fiber chimerism for effective adenoviral oncolysis in breast cancer.

Conditionally replicative adenoviruses (CRAds) represent novel therapeutic agents that have been recently applied in the context of breast cancer therapy. However, deficiencies in the ability of the adenovirus to infect target tumor cells and to specifically replicate within the tumor target represent key deficiencies preventing the realization of the full potential of this therapeutic approach. Minimal expression of the adenovirus serotype 5 (Ad5) receptor CAR (coxsackie and adenovirus receptor) on breast cancer cells represents a major limitation for Ad5-based virotherapy. Genetic fiber chimerism is a method to alter the tropism of Ad5-based CRAds to achieve CAR-independent infectivity of tumor cells. Here, we describe the use of a CRAd with cancer specific transcriptional control of the essential Ad5 E1A gene using the human CXCR4 gene promoter. We further modified the fiber protein of this agent by switching the knob domain with that of the adenovirus serotype 3. The oncolytic activity of this 5/3 fiber-modified CRAd was studied in breast cancer cell lines, primary breast cancer and human liver tissue slices from patients, and in a xenograft breast cancer mouse model. This infectivity enhanced CRAd agent showed improved replication and killing in breast cancer cells in vitro and in vivo with a remarkable specificity profile that was strongly attenuated in nonbreast cancer cells, as well as in normal human breast and liver tissues. In conclusion, utilization of a CRAd that combined infectivity enhancement strategies and transcriptional targeting improved the CRAd-based antineoplastic effects for breast cancer therapy.

Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma.

PURPOSE: Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to inefficient virus delivery to the tumor site. The present study addresses the utility of human mesenchymal stem cells (hMSCs) as intermediate carriers for conditionally replicating adenoviruses (CRAds) to target metastatic breast cancer in vivo. EXPERIMENTAL DESIGN: HMSC were transduced with CRAds. We used a SCID mouse xenograft model to examine the effects of systemically injected CRAd loaded hMSC or CRAd alone on the growth of MDA-MB-231 derived pulmonary metastases (experimental metastases model) in vivo and on overall survival. RESULTS: Intravenous injection of CRAd loaded hMSCs into mice with established MDA-MB-231 pulmonary metastatic disease homed to the tumor site and led to extended mouse survival compared to mice treated with CRAd alone. CONCLUSION: Injected hMSCs transduced with CRAds suppressed the growth of pulmonary metastases, presumably through viral amplification in the hMSCs. Thus, hMSCs may be an effective platform for the targeted delivery of CRAds to distant cancer sites such as metastatic breast cancer.

Abdominoplasty with total abdominal liposuction for patients with massive weight loss.

BACKGROUND: Massive weight loss after bariatric surgery is associated with significant skin excess, laxity, and ptosis over the abdomen. Good results have been achieved with abdominoplasty and circumferential lipectomy. However, blood transfusions are sometimes needed, and patients may require long hospital stays. Furthermore, morbidity rates are high. Total abdominal liposuction performed with abdominoplasty allows for the preservation of lymphatic vessels below Scarpa's fascia and eliminates the need for upper flap undermining. This study aimed to evaluate this technique in patients with anterior abdominal redundancy attributable to massive weight loss after bariatric surgery. METHODS: The charts of 60 patients treated between December 2001 and October 2004 were retrospectively reviewed. All the patients had undergone previous bariatric surgery as well as subsequent total abdominal liposuction and abdominoplasty. RESULTS: The average amount of wetting solution used was 3.1 l, and the average total aspirate was 2.5 l. The mean pannus weight was 3,649 g, and the average dimension was 48 x 25 x 6 cm. No patient required a blood transfusion. The median in-hospital stay was 1 day, with 42% of the patients treated as outpatients. The median follow-up period was 3 months. Morbidity was 22%. Factors associated with the development of complications were weight of the pannus, transverse dimension of the pannus, and body mass index. All the patients were satisfied with the results. CONCLUSIONS: Total abdominal liposuction followed by abdominoplasty is adequate treatment for anterior abdominal redundancy for patients with massive weight loss.

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds.

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.

Modulation of myocardial contractility by lysophosphatidic acid (LPA).

Lysophosphatidic acid (LPA) is a phospholipid messenger, which is released from activated platelets and leukocytes. This study examined the effects of LPA on myocardial contractility and characterized the signal transduction pathway involved in these effects. Functional effects of LPA were determined in isolated, electrically driven human myocardial preparations and rat cardiac myocytes. In human atrial and ventricular myocardial preparations, LPA (100 micromol/l) decreased isoprenaline (0.03 micromol/l) enhanced force of contraction by 17 +/- 2% and 28 +/- 3%, respectively. The effect of LPA was attenuated by suramin (1 mmol/l). In isolated rat cardiomyocytes, LPA (1-100 micromol/l) concentration dependently abolished isoprenaline (0.03 micromol/l) induced increase in cell shortening. This antiadrenergic effect was blunted after pretreatment with pertussis toxin (5 microg/ml, 12 h). Forskolin (10 micromol/l) stimulated adenylyl cyclase activity was inhibited by LPA in human myocardial membranes. PCR analysis of human atrial and ventricular cDNAs revealed the expression of two cognate LPA receptors: EDG-2 and EDG-7. Our results suggest that LPA exerts antiadrenergic effects on force of contraction in human and rodent myocardium via a Galpha(i/o) protein-mediated mechanism, most probably by LPA binding to the mammalian LPA receptors EDG-2 and/or EDG-7. This newly discovered action of LPA might be of pathophysiological importance in conditions like myocardial ischemia or inflammatory disorders when LPA release is enhanced.