Radiological Analysis of the Syndesmosis Concept in Metatarsus Primus Varus and Hallux Valgus Deformities Recurrence Prevention.

Hallux valgus (HV) is a common deformity of the foot. Its postoperative recurrence is not uncommon and is closely related to the recurrence of its underlying metatarsus primus varus (MPV) deformity. The syndesmosis procedure uses 1 to 2 intermetatarsal cerclage sutures to realign the first metatarsal and then induces a biological bonding between the 2 metatarsals to prevent the MPV deformity from recurring. This radiological study aimed to assess its effectiveness in long-term MPV and HV deformities recurrence prevention. Ninety-two feet of 51 consecutive patients had syndesmosis procedures that were prospectively followed up for more than 1 y and up to 14 y, averaging 100.5 (SD 45.2) months. Patients underwent X-ray examinations regularly at fixed intervals of their feet. We used Hardy's methods in measuring the intermetatarsal angle (IMA), hallux valgus angle (HVA), and medial sesamoid position from standing foot X-rays. More than 450 relevant X-ray and photo images were submitted as Supplementary Material for online viewing and reference. There was a significant final correction of IMA from 14.30° (SD 2.70) to 6.70° (SD 1.75) (p < .0001). There was no significant increase in IMA after the sixth postoperative month to their final follow-up endpoints, regardless of their lengths. There was a significant final correction of HVA from 31.95° (SD 7.45) to 19.1° (SD 7.45) (p < .0001). This study reconfirmed past findings that the MPV deformity could be corrected without osteotomies. Creating a syndesmosis-like intermetatarsal bonding was effective for long-term MPV recurrence prevention. Three feet had postoperative stress fracture of the second metatarsal. However, the HV deformity correction was less satisfactory, and the reasons were explained.

Reciprocal c-di-GMP signaling: Incomplete flagellum biogenesis triggers c-di-GMP signaling pathways that promote biofilm formation.

The assembly status of the V. cholerae flagellum regulates biofilm formation, suggesting that the bacterium senses a lack of movement to commit to a sessile lifestyle. Motility and biofilm formation are inversely regulated by the second messenger molecule cyclic dimeric guanosine monophosphate (c-di-GMP). Therefore, we sought to define the flagellum-associated c-di-GMP-mediated signaling pathways that regulate the transition from a motile to a sessile state. Here we report that elimination of the flagellum, via loss of the FlaA flagellin, results in a flagellum-dependent biofilm regulatory (FDBR) response, which elevates cellular c-di-GMP levels, increases biofilm gene expression, and enhances biofilm formation. The strength of the FDBR response is linked with status of the flagellar stator: it can be reversed by deletion of the T ring component MotX, and reduced by mutations altering either the Na+ binding ability of the stator or the Na+ motive force. Absence of the stator also results in reduction of mannose-sensitive hemagglutinin (MSHA) pilus levels on the cell surface, suggesting interconnectivity of signal transduction pathways involved in biofilm formation. Strains lacking flagellar rotor components similarly launched an FDBR response, however this was independent of the status of assembly of the flagellar stator. We found that the FDBR response requires at least three specific diguanylate cyclases that contribute to increased c-di-GMP levels, and propose that activation of biofilm formation during this response relies on c-di-GMP-dependent activation of positive regulators of biofilm production. Together our results dissect how flagellum assembly activates c-di-GMP signaling circuits, and how V. cholerae utilizes these signals to transition from a motile to a sessile state.

Improving Communication in a Large Urban Academic Safety Net Hospital System: Implementation of Secure Messaging.

Given the complexities of communication within health systems, we investigated how the implementation of secure messaging in addition to traditional paging would impact hospital communication. This study was implemented at Grady Health System (GHS), a large safety net academic hospital system in metro Atlanta that includes inpatient and ambulatory settings. GHS uses Epic Electronic Health Record (EHR), and secure messaging was performed using Epic Haiku Platform. To assess states of communication, we implemented pre- and post-surveys. The secure messaging data tracked from 2018 to 2022 demonstrated a rise in usage from 9,378 chats per month when it went live in August 2018 to greater than 200,000 monthly messages during the pandemic when social distancing measures were enacted. Monthly usage peaked in March 2022 with 378,932 messages. Pre-and-post survey questions using a Likert scale (1-4) showed increased agreement in the ability to reach all team members through secure chat amongst healthcare workers. Within our unit staff, communication improved by being more rapid and reliable, as the Likert scale means increased from 2.18 pre-survey to 2.63 post survey. Pre-and-post survey analysis indicates improved satisfaction across GHS stakeholders with the implementation of secure chat in addition to the existing direct-paging system. Next steps could include exchanging digital media through secure messaging to facilitate faster diagnosis and treatment of certain medical conditions. Secure messaging integrated within the EHR (including mobile devices) enhances communication between healthcare team members in a HIPAA-compliant way reducing the number of pages and phone calls.

The Syndesmosis Procedure Correction of Hallux Valgus Feet Associated With the Metatarsus Adductus Deformity.

Metatarsus adductus and hallux valgus are common foot deformities. Corrective surgery of hallux valgus feet with metatarsus adductus deformity can be challenging and experience a high deformity recurrence rate. The purpose of this study was to demonstrate if the syndesmosis procedure can correct such feet satisfactorily without osteotomies and arthrodesis. 75 hallux valgus feet in 45 patients with a Sgarlato's metatarsal adductus angle ≥15° were studied after having undergone the syndesmosis procedure for an average of 20.22 months. Their average preoperative intermetatarsal angle of 12.56° was improved to 6.00° (p < .001) and metatarsophalangeal angle from 35.61° to 23.46° (p < .001) significantly. Their average American Orthopedic Foot and Ankle Society's clinical scores improved significantly from 56.41 to 90.53 points (p < .001). Fifty-five feet (73.33%) had preoperative metatarsal calluses, and all but 3 had a noticeable reduction in severity. Forty-one patients (91.11%) were able to return to their desired activities and footwear. All relevant raw data formed this study, including x-ray and photographic images, were submitted as Supplementary Material for online viewing and reference. Despite the possible intrinsic rigidity of metatarsus adductus forefoot, this study demonstrated that hallux valgus feet with metatarsus adductus deformity could be corrected anatomically and functionally with the soft tissue syndesmosis procedure and without correcting the preexisting metatarsus adductus deformity. This study also supports the notion that the MA deformity accentuates hallux valgus alignment preoperatively and postoperatively, and possibly all feet in general.

Role of t-tubule remodeling on mechanisms of abnormal calcium release during heart failure development in canine ventricle.

The goal of this work was to investigate the role of t-tubule (TT) remodeling in abnormal Ca2+ cycling in ventricular myocytes of failing dog hearts. Heart failure (HF) was induced using rapid right ventricular pacing. Extensive changes in echocardiographic parameters, including left and right ventricular dilation and systolic dysfunction, diastolic dysfunction, elevated left ventricular filling pressures, and abnormal cardiac mechanics, indicated that severe HF developed. TT loss was extensive when measured as the density of total cell volume, derived from three-dimensional confocal image analysis, and significantly increased the distances in the cell interior to closest cell membrane. Changes in Ca2+ transients indicated increases in heterogeneity of Ca2+ release along the cell length. When critical properties of Ca2+ release variability were plotted as a function of TT organization, there was a complex, nonlinear relationship between impaired calcium release and decreasing TT organization below a certain threshold of TT organization leading to increased sensitivity in Ca2+ release below a TT density threshold of 1.5%. The loss of TTs was also associated with a greater incidence of triggered Ca2+ waves during rapid pacing. Finally, virtually all of these observations were replicated by acute detubulation by formamide treatment, indicating an important role of TT remodeling in impaired Ca2+ cycling. We conclude that TT remodeling itself is a major contributor to abnormal Ca2+ cycling in HF, reducing myocardial performance. The loss of TTs is also responsible for a greater incidence of triggered Ca2+ waves that may play a role in ventricular arrhythmias arising in HF.NEW & NOTEWORTHY Three-dimensional analysis of t-tubule density showed t-tubule disruption throughout the whole myocyte in failing dog ventricle. A double-linear relationship between Ca2+ release and t-tubule density displays a steeper slope at t-tubule densities below a threshold value (∼1.5%) above which there is little effect on Ca2+ release (T-tubule reserve). T-tubule loss increases incidence of triggered Ca2+ waves. Chemically induced t-tubule disruption suggests that t-tubule loss alone is a critical component of abnormal Ca2+ cycling in heart failure.

p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration.

Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia or acute respiratory distress syndrome often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process. Here we show that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.

Exploring injury intentionality and mechanism via ICD-10-CM injury codes and self-reported injury in a large, urban emergency department.

Health systems capture injuries using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification (ICD-10-CM) diagnostic codes and share data with public health to inform injury surveillance. This study analyses provider-assigned ICD-10-CM injury codes among self-reported injuries to determine the effectiveness of ICD-10-CM coding in capturing injury and assault. METHODS: Self-reported injury screen records from an urban, level 1 trauma centre collected between 20 November 2015 and 30 September 2019 were compared with corresponding provider-assigned ICD-10-CM codes discerning the frequency in which intentions are indicated among patients reporting (1) any injury and (2) assault. RESULTS: Of 380 922 patients screened, 32 788 (8.61%) reported any injury and 6763 (1.78%) reported assault. ICD-10-CM codes had a sensitivity of 67.40% (95% CI 66.89% to 67.91%) for any injury and specificity of 89.79% (95% CI 89.69% to 89.89%]). For assault, ICD-10-CM codes had sensitivity of 2.25% (95% CI 1.91% to 2.63%) and specificity of 99.97% (95% CI 99.97% 99.98%). DISCUSSION: This study found provider-assigned ICD-10-CM had limited sensitivity to identify injury and low sensitivity for assault. This study more fully characterises ICD-10-CM coding system effectiveness in identifying assaults.

A prospective cross-sectional study examining the documented evaluation of patients at high risk for mild traumatic brain injury.

OBJECTIVES: Annually, the CDC reports that 2.5 million Emergency Department (ED) visits occur due to Traumatic Brain Injuries (TBI) with nearly 75% classified as mild TBI (mTBI). Generally, these injuries are thought to be under recognized. This study was done to determine the proportion of patients, who were considered high risk for an mTBI, that had documentation of an mTBI evaluation. METHODS: A prospective cross-section of patients was identified using a 3-question screen at the time of triage: did an injury occur; was the mechanism consistent with mTBI; and was there a period of altered mental status. Chart review was completed for these patients who were thought to meet a minimum threshold warranting an evaluation for mTBI. RESULTS: 38,621 patients were screened over 16 weeks, of whom 441 (1.14%) were identified as being high risk for having an mTBI and met inclusion criteria. Recommended portions of an mTBI evaluation occurred in fewer than 50% of patients. In total, 98 subjects were diagnosed with an mTBI, and 49 received mTBI discharge instructions. The odds ratio for the subgroup of patients who had documented criteria sufficient for diagnosis revealed that an isolated head injury increased a patient's odds of a documented diagnosis by 2.1 times (95%, 1.3-3.4). CONCLUSIONS: Many patients with a possible mTBI did not have significant portions of an mTBI evaluation documented, and roughly half of the patients with a documented mTBI diagnosis did not receive discharge education. Changes in clinicians' approach to mTBI must occur to ensure patients receive appropriate evaluations, management, and education.

Concussion Care in the Emergency Department: A Prospective Observational Brief Report.

STUDY OBJECTIVE: Emergency physicians are often the initial-and only-clinical providers for patients who have sustained a mild traumatic brain injury. This prospective observational study seeks to examine the practice patterns of clinicians in an academic Level I trauma center as they relate to the evaluation of patients who were presumed to be at high risk for mild traumatic brain injury. Specifically, we describe the frequency of a documented mild traumatic brain injury evaluation, diagnosis, and discharge education. METHODS: This pilot study took place in a single academic Level I trauma and emergency care center during a 4-week period. Patients were identified by triage nurses, who determined whether they responded affirmatively to 2 questions that indicated a potential risk for mild traumatic brain injury. Data were abstracted from emergency department clinician documentation on identified patients to describe the frequency of a documented mild traumatic brain injury evaluation (history and physical examination), diagnosis, and discharge education among those who were identified to be at risk for a mild traumatic brain injury. RESULTS: Ninety-eight subjects were included in the present study. Documentation of a mild traumatic brain injury evaluation was present for less than 50% of patients, a final diagnosis of mild traumatic brain injury was included for 36 (37%; 95% confidence interval 27.8% to 46.7%), and discharge education was provided to 15 (15%; 95% confidence interval 9.2% to 21.4%). Of the 36 patients who received a documented mild traumatic brain injury diagnosis, 15 (41.5%; 95% confidence interval 26.7% to 57.9%) received mild traumatic brain injury-specific discharge education. CONCLUSION: This study suggests that the majority of patients at high risk for mild traumatic brain injury have no documentation of an evaluation for one. Also, patients with a mild traumatic brain injury diagnosis were unlikely to receive appropriate discharge education about it. Education and standardization are needed to ensure that patients at risk for mild traumatic brain injury receive appropriate evaluation and care.

Building capacity for injury prevention: a process evaluation of a replication of the Cardiff Violence Prevention Programme in the Southeastern USA.

OBJECTIVES: Violence is a major public health problem in the USA. In 2016, more than 1.6 million assault-related injuries were treated in US emergency departments (EDs). Unfortunately, information about the magnitude and patterns of violent incidents is often incomplete and underreported to law enforcement (LE). In an effort to identify more complete information on violence for the development of prevention programme, a cross-sectoral Cardiff Violence Prevention Programme (Cardiff Model) partnership was established at a large, urban ED with a level I trauma designation and local metropolitan LE agency in the Atlanta, Georgia metropolitan area. The Cardiff Model is a promising violence prevention approach that promotes combining injury data from hospitals and LE. The objective was to describe the Cardiff Model implementation and collaboration between hospital and LE partners. METHODS: The Cardiff Model was replicated in the USA. A process evaluation was conducted by reviewing project materials, nurse surveys and interviews and ED-LE records. RESULTS: Cardiff Model replication centred around four activities: (1) collaboration between the hospital and LE to form a community safety partnership locally called the US Injury Prevention Partnership; (2) building hospital capacity for data collection; (3) data aggregation and analysis and (4) developing and implementing violence prevention interventions based on the data. CONCLUSIONS: The Cardiff Model can be implemented in the USA for sustainable violent injury data surveillance and sharing. Key components include building a strong ED-LE partnership, communicating with each other and hospital staff, engaging in capacity building and sustainability planning.

Sequential implementation of the EQUIPPED geriatric medication safety program as a learning health system.

OBJECTIVES: To present the three-site EQUIPPED academic health system research collaborative, which engaged in sequential implementation of the EQUIPPED medication safety program, as a learning health system; to understand how the organizations worked together to build resources for program scale-up. DESIGN: Following the Replicating Effective Programs framework, we analyzed content from implementation teams' focus groups, local and cross-site meeting minutes and sites' organizational profiles to develop an implementation package. SETTING: Three academic emergency departments that each implemented EQUIPPED over three successive years. PARTICIPANTS: Implementation team members at each site participating in focus groups (n = 18), local meetings during implementation years, and cross-site meetings during all years of the projects. INTERVENTION(S): EQUIPPED provides Emergency Department providers with clinical decision support (education, order sets, and feedback) to reduce prescribing of potentially inappropriate medications to adults aged 65 years and older who received a prescription at time of discharge. MAIN OUTCOME MEASURE(S): Implementation process components assembled through successive implementation. RESULTS: Each site had clinical and environmental characteristics to be addressed in implementing the EQUIPPED program. We identified 10 process elements and describe lessons for each. Lessons guided the compilation of the EQUIPPED intervention package or toolkit, including the EQUIPPED logic model. CONCLUSIONS: Our academic health system research collaborative addressing medication safety through sequential implementation is a learning health system that can serve as a model for other quality improvement projects with multiple sites. The network produced an implementation package that can be vetted, piloted, evaluated, and finalized for large-scale dissemination in community-based settings.

NtrC Adds a New Node to the Complex Regulatory Network of Biofilm Formation and vps Expression in Vibrio cholerae.

The biofilm growth mode is important in both the intestinal and environmental phases of the Vibrio cholerae life cycle. Regulation of biofilm formation involves several transcriptional regulators and alternative sigma factors. One such factor is the alternative sigma factor RpoN, which positively regulates biofilm formation. RpoN requires bacterial enhancer-binding proteins (bEBPs) to initiate transcription. The V. cholerae genome encodes seven bEBPs (LuxO, VC1522, VC1926 [DctD-1], FlrC, NtrC, VCA0142 [DctD-2], and PgtA) that belong to the NtrC family of response regulators (RRs) of two-component regulatory systems. The contribution of these regulators to biofilm formation is not well understood. In this study, we analyzed biofilm formation and the regulation of vpsL expression by RpoN activators. Mutants lacking NtrC had increased biofilm formation and vpsL expression. NtrC negatively regulates the expression of core regulators of biofilm formation (vpsR, vpsT, and hapR). NtrC from V. cholerae supported growth and activated glnA expression when nitrogen availability was limited. However, the repressive activity of NtrC toward vpsL expression was not affected by the nitrogen sources present. This study unveils the role of NtrC as a regulator of vps expression and biofilm formation in V. choleraeIMPORTANCE Biofilms play an important role in the Vibrio cholerae life cycle, contributing to both environmental survival and transmission to a human host. Identifying key regulators of V. cholerae biofilm formation is necessary to fully understand how this important growth mode is modulated in response to various signals encountered in the environment and the host. In this study, we characterized the role of RRs that function as coactivators of RpoN in regulating biofilm formation and identified new components in the V. cholerae biofilm regulatory circuitry.

Reversible Control of Protein Localization in Living Cells Using a Photocaged-Photocleavable Chemical Dimerizer.

Many dynamic biological processes are regulated by protein-protein interactions and protein localization. Experimental techniques to probe such processes with temporal and spatial precision include photoactivatable proteins and chemically induced dimerization (CID) of proteins. CID has been used to study several cellular events, especially cell signaling networks, which are often reversible. However, chemical dimerizers that can be both rapidly activated and deactivated with high spatiotemporal resolution are currently limited. Herein, we present a novel chemical inducer of protein dimerization that can be rapidly turned on and off using single pulses of light at two orthogonal wavelengths. We demonstrate the utility of this molecule by controlling peroxisome transport and mitotic checkpoint signaling in living cells. Our system highlights and enhances the spatiotemporal control offered by CID. This tool addresses biological questions on subcellular levels by controlling protein-protein interactions.

ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels.

OBJECTIVE: High-density lipoproteins (HDL) are considered to protect against atherosclerosis in part by facilitating the removal of cholesterol from peripheral tissues. However, factors regulating lipid efflux are incompletely understood. We previously identified a variant in adenosine triphosphate-binding cassette transporter A8 (ABCA8) in an individual with low HDL cholesterol (HDLc). Here, we investigate the role of ABCA8 in cholesterol efflux and in regulating HDLc levels. APPROACH AND RESULTS: We sequenced ABCA8 in individuals with low and high HDLc and identified, exclusively in low HDLc probands, 3 predicted deleterious heterozygous ABCA8 mutations (p.Pro609Arg [P609R], IVS17-2 A>G and p.Thr741Stop [T741X]). HDLc levels were lower in heterozygous mutation carriers compared with first-degree family controls (0.86±0.34 versus 1.17±0.26 mmol/L; P=0.005). HDLc levels were significantly decreased by 29% (P=0.01) in Abca8b-/- mice on a high-cholesterol diet compared with wild-type mice, whereas hepatic overexpression of human ABCA8 in mice resulted in significant increases in plasma HDLc and the first steps of macrophage-to-feces reverse cholesterol transport. Overexpression of wild-type but not mutant ABCA8 resulted in a significant increase (1.8-fold; P=0.01) of cholesterol efflux to apolipoprotein AI in vitro. ABCA8 colocalizes and interacts with adenosine triphosphate-binding cassette transporter A1 and further potentiates adenosine triphosphate-binding cassette transporter A1-mediated cholesterol efflux. CONCLUSIONS: ABCA8 facilitates cholesterol efflux and modulates HDLc levels in humans and mice.

Can the Syndesmosis Procedure Prevent Metatarsus Primus Varus and Hallux Valgus Deformity Recurrence? A 5-Year Prospective Study.

One of the main objectives of hallux valgus surgery is correction of the metatarsus primus varus deformity by osteotomy, arthrodesis, or soft tissue correction. The syndesmosis procedure uses intermetatarsal cerclage sutures to realign the first metatarsal and also induces a syndesmotic bonding between the first and second metatarsals to prevent metatarsus primus varus deformity recurrence. The purpose of the present study was to demonstrate radiologic evidence of the effectiveness of the syndesmosis concept and to identify the incidence and nature of deformity recurrence. A total of 55 feet from 60 consecutive procedures were followed regularly at 6 fixed points for 5 years. The radiologic inclusion criterion was a first intermetatarsal angle >9° or metatarsophalangeal angle >20°. The initial postoperative radiographs showed significant correction of the intermetatarsal angle from a preoperative average of 14.5° to 4.3° (p < .0001). It had increased to 7.0° during the first 6 postoperative months but remained within the normal upper limit of 9° and exhibited no further significant changes for the subsequent 4.5 years (p = .0792). Hallux valgus deformity correction also correlated with metatarsus primus varus deformity correction. Three (5%) second metatarsal stress fractures occurred, and all recovered uneventfully. In conclusion, we have report the findings from a detailed medium long-term follow-up study showing, to the best of our knowledge, for the first time that metatarsus primus varus and hallux valgus deformities can be effectively corrected and maintained using a specific surgical technique. Also included are 6 relevant radiographs and photographs of the included and excluded feet in the online Supplementary Material for reference.

The Unusual Presence of Gas From a Puncture Wound: A Case Report.

The presence of gas within soft tissues as suggested by plain film radiographs and magnetic resonance imaging is usually sufficient evidence for a gas-producing bacterial infection. A thorough clinical examination and history and tissue culture are necessary to better determine the source of the gas. However, despite the unremarkable physical examination findings, the present case of a plantar puncture wound rapidly developed gas in the tissues and warranted surgical exploration and repair. Delaying treatment in any case of potential gas gangrene can be limb- and life-threatening. Only later was it revealed by the patient's husband that the wound might have been contaminated soon after the injury from a source other than the puncture, which led to the early presentation of gas on the imaging studies.

Case report: An HIV+ patient presenting with pancytopenia, hepatic failure, and coagulopathy; a rare small cell liver carcinoma with diffuse splenic and bone marrow metastasis diagnosed at autopsy.

A 34-year old male with a giant condyloma acuminatum of the anus secondary to HIV infection presented to the emergency department with a persistent nose bleed lasting 2-3days, acute anemia, thrombocytopenia, and coagulopathy. The patient also had significant hepatosplenomegaly and elevated liver enzymes which were a new finding since the patient's last hospitalization 1-2month prior to the current admission. A bone marrow biopsy showed diffuse infiltration by carcinoma with neuroendocrine features. The patient quickly developed multi-organ injury, decompensated, and died. An autopsy was obtained which established the diagnosis of small cell carcinoma of the liver.

Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61.

Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low-density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation. By using LPA infusion of carotid artery in a mouse model, we demonstrated that LPA highly induced CCN1 expression (approximately six- to sevenfold) in neointimal lesions. Downregulation of CCN1 expression with the specific CCN1 siRNA in carotid arteries blocked LPA-induced neointimal formation, indicating that CCN1 is essential in LPA-induced neointimal formation. We then used LPA receptor knockout (LPA1-/-, LPA2-/-, and LPA3-/-) mice to examine LPA receptor function in CCN1 expression in vivo and in LPA-induced neointimal formation. Our data reveal that LPA1 deficiency, but not LPA2 or LPA3 deficiency, prevents LPA-induced CCN1 expression in vivo in mouse carotid arteries. We also observed that LPA1 deficiency blunted LPA infusion-induced neointimal formation, indicating that LPA1 is the major mediator for LPA-induced vascular remodeling. Our in vivo model of LPA-induced neointimal formation established a key role of the ECM protein CCN1 in mediating LPA-induced neointimal formation. Our data support the notion that the LPA1-CCN1 axis may be the central control for SMC migration and vascular remodeling. CCN1 may serve as an important vascular disease marker and potential target for vascular therapeutic intervention.