, January 27, 2011, Michael O’Riordan

(Miami Beach, Florida) — Should patients at standard risk for adverse events from carotid endarterectomy be treated with carotid artery stenting? That is the question a Food and Drug Administration (FDA) advisory panel grappled with this past Wednesday, as panel members gathered to make recommendations and vote on an expanded indication for the RX Acculink Carotid Stent System (Abbott, Abbott Park, IL) [1].

Currently, the RX Acculink stent is approved for use in patients requiring carotid revascularization who are at high risk for adverse events from carotid endarterectomy. These high-risk patients must also have a reference vessel diameter ranging from 4.0 mm to 9.0 mm at the target lesion and be symptomatic with a stenosis of the common or internal carotid artery >50%. The stent is also approved in high-risk patients without neurological symptoms but who have a stenosis of the common or internal carotid artery >80%.

Based on data from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), Abbott is looking to expand the indication of the RX Acculink stent to include patients at standard risk for adverse events from carotid surgery. Patients must meet the same criteria as high-risk patients, but the company is also seeking approval for use in asymptomatic patients with a stenosis >70%, as opposed to >80% with the current indication.

We believe there are data suggesting that, in patients in all risk stratifications, stenting is safe and effective.

“The CREST study gave us a tremendous amount of data, some of which will be presented to the FDA,” Dr James Benenati (Baptist Heart and Vascular Institute, Miami, FL), president of the Society of Interventional Radiologists (SIR), told heartwire last week at the International Symposium on Endovascular Therapy (ISET) 2011. “Basically, in carotid stenting in general, we know that for high-risk symptomatic patients, the FDA has approved this procedure. What many of us in the interventional community are looking for is an expansion. We believe there are data suggesting that, in patients in all risk stratifications, stenting is safe and effective, and the differences between endarterectomy and stenting in all patient subgroups are basically very, very small.”

Based on the FDA briefing materials, the hopes of Benenati and others in the interventional community are supported by the agency. According to an executive summary released early by the FDA, the new “proposed indications are supported by a primary analysis of the CREST trial data and by multiple important secondary and tertiary analyses.”

The FDA Circulatory System Devices advisory panel will be chaired by Dr Jeffrey Borer (University of Pennsylvania, PA), who participates in the voting process with 12 other panel members. During the day-long meeting, panel members are expected to discuss the appropriateness of the RX Acculink device in octogenarians and nonoctogenarians and in symptomatic and asymptomatic patients, as well as likely to discuss the relative role of operator experience in achieving favorable results. The briefing documents are available here.

Treating Asymptomatic Patients

Although large portions of the FDA document are blacked out and won’t be made public until Wednesday during the advisory panel meeting, the agency notes that primary-end-point event rates are lower than acceptable event rates proposed by the American Heart Association (AHA) guidelines for carotid revascularization. For example, the combined end point of periprocedural death and stroke in CREST was 5.9% for carotid stenting and 2.4% for carotid endarterectomy in symptomatic patients, lower than the AHA-acceptable standard of 6%, although it’s close to the limit for carotid stenting. In asymptomatic patients, the AHA-proposed limit for periprocedural death and stroke is 3%, and in CREST both the carotid stenting and endarterectomy arms fell below this limit (2.5% vs 1.3%, respectively).

Speaking at ISET last week, however, were some who believed that asymptomatic patients shouldn’t be treated with stents or surgery at all but rather with medical therapy. In an interview with heartwire , Dr Anthony Comerota (University of Michigan, Ann Arbor) said that the “overwhelming majority” of patients in the US who undergo carotid stenting do not have any symptoms. Good medical management–such as high-dose statin therapy, good blood-pressure control, management of diabetes, and good platelet inhibition–can reduce the risk of stroke, and carotid endarterectomy, as well as carotid stenting, should be best left to highly selected patients, said Comerota.

I wouldn’t advocate that everybody gets a carotid stent, nor would I advocate that every carotid stenosis be treated with stent or surgery.

Speaking at ISET, Comerota said that 97% of carotid-etiology strokes occur in patients with symptomatic disease, and yet 2005 data showed that more than 90% of carotid revascularization procedures were performed in asymptomatic patients. The reason this is important is that the biological characteristics of symptomatic and asymptomatic plaque differ significantly, with symptomatic plaque being more unstable, showing evidence of subintimal hemorrhage and thrombus within the lumen.

Benenati agreed, saying that while candidates for surgery should also be candidates for carotid stenting, not every patient is a candidate for revascularization.

“I wouldn’t advocate that everybody gets a carotid stent, nor would I advocate that every carotid stenosis be treated with stent or surgery,” he told heartwire . “One of the great things that all the carotid stent trials have brought to light is that there are some groups of patients that might do better with medical therapy. For example, asymptomatic patients, high- and low-risk, with stenosis less than 70% or 80%, will probably do fine with medical therapy.”

The Primary End Point in CREST

Although the expanded RX Acculink indication is based on data from CREST, Comerota took issue with the study, saying that the design incorporated an “inherent fallacy” that was part of conventional thinking at the time the trial was started. The primary end point was a composite of clinical stroke, MI, or death during the periprocedural period plus ipsilateral stroke on the vessel that was treated, with patients followed out to four years. At the time, perioperative MI was thought to be a very important problem, Comerota told heartwire , one that led to a significantly higher death rate at six months.

So now we have a major trial equating an elevation in cardiac enzymes with stroke or death.

“This has turned out not to be the case,” he said. “An asymptomatic myocardial infarction, a troponin leak, is not associated with an increased mortality risk and is not associated prognostically with an increased mortality risk over the next four or five years. So now we have a major trial equating an elevation in cardiac enzymes with stroke or death. That clearly is inappropriate, but when enthusiasts of carotid angioplasty and stenting want to present their side of the story, they’ll say there is no difference because of the higher myocardial infarction rate [with surgery]. Myocardial infarction didn’t alter the quality of life of patients down the road, whereas stroke, even minor stroke, altered the quality of life significantly.”

In CREST, as reported previously by heartwire , there was no significant difference in the combined end point of stroke, MI, or death within the periprocedural period (7.2% for carotid stenting vs 6.8% for endarterectomy; p=0.51), but stroke rates were higher in the stenting arm, while rates of MI were higher among the surgical patients.

Based on the FDA documents, the advisory panel will discuss the appropriateness of including MI in the primary end point, as well as its definition and impact on the primary end point. In addition, they will debate the clinical significance and severity of cranial nerve injury, which occurred in 5.2% of patients treated with endarterectomy.

First the FDA Hurdle, Next the CMS

At the end of the day, even if the FDA advisory panel votes to approve the expanded indication for the RX Acculink stent to include standard-risk surgical patients, the Centers for Medicare and Medicaid Services (CMS) still need to green-light reimbursement. Currently, Medicare coverage is confined to patients at high risk for carotid endarterectomy who have symptomatic carotid artery stenosis >70%, as long as stenting is performed using FDA-approved systems with embolic-protection devices and at CMS-approved facilities. The CMS also covers carotid stenting in patients if they are a high-risk endarterectomy patient with lesser degrees of symptomatic carotid artery stenosis (50% to 70%) or at high risk for endarterectomy with asymptomatic carotid artery stenosis >80%, but only if they are participating in pre- or postapproval studies.

To heartwire , Benenati said the day is coming when clinical centers performing carotid stenting will need to receive accreditation. The Intersocietal Commission for the Accreditation of Carotid Stenting Procedures, in support of numerous societies, including SIR, is seeking to establish minimum requirements and recommendations for facilities performing carotid stenting.

“I’m a strong advocate, as is the society, that not every physician who does endovascular therapy should be doing carotid stenting,” said Benenati. “Carotid stenting is a skill that’s learned–it takes repetition and dedicated continuing medical education. Also, the facility where the carotid stenting takes place is critically important, too.”

Benenati reports serving as the chief medical officer of Northpoint Domain and consulting for or serving on the advisory boards of Abbott, Amaranth Medical, Biosphere, Cordis, Endovention, and WL Gore. Comerota reports speaking for or receiving honoraria from Bristol-Myers Squibb, Covidien, Otsuka, Sanofi-Aventis, Servier, ZymoGenetics; consulting for or serving on the advisory boards of Aastrom, AngioDynamics, Convatec, Cook, Covidien, Bristol-Myers Squibb, Talecris; and receiving research support from Aastrom, Abbott Vascular, Baxter, Bristol-Myers Squibb, Boehringer Ingelheim, BSN, Colorado Prevention Center, CVRx, eV3, Johnson & Johnson, Lombard Medical, Medtronic, the National Institutes of Health, Pfizer, Sanofi-Aventis, Schering-Plough, and Talecris.

More About Carotid Stenting

The two common carotid arteries bring oxygenated blood from the heart through the neck to each side of the head. As people age, plaque can build up inside their arteries. Over time, these plaques collect on arterial walls as cholesterol circulates in the blood. As the plaques enlarge, the arteries become narrow and stiff, a process called atherosclerosis, or “hardening of the arteries.”

Blood clots forming on the plaque can cause an occlusion or blockage, preventing the flow of blood to the brain. The blockage can create an ischemia, or lack of oxygen caused by insufficient blood flow, which can cause an ischemic stroke if the blood flow is blocked long enough.

Atherosclerotic plaques in the carotid arteries can also increase a person’s risk of an arterial embolism, the sudden blocking of an artery by a small piece of loose plaque or a loose blood clot.

Carotid stenting is a procedure in which a tiny, slender metal-mesh tube is fitted inside a carotid artery to increase the flow of blood blocked by plaques. The stent is inserted following a procedure called angioplasty, in which the physician guides a balloon-tipped catheter into the blocked artery. The balloon is inflated and presses against the plaque, flattening it and re-opening the artery. The stent acts as scaffolding to prevent the artery from collapsing or being closed by plaque after the procedure is completed.


Stenting is often recommended for people who are unable to undergo an endarterectomy. Endarterectomy, the surgical removal of plaque from the artery, is the standard treatment for severe buildup of plaque in the carotid artery. For some people, however, endarterectomy may not be appropriate. For example, the procedure is inappropriate for people who are unable to tolerate the side effects of anesthesia.

Common conditions that make endarterectomy high risk include:

  • Advanced age or the presence of serious disease, such as cancer;
  • Surgically inaccessible atherosclerotic plaques;
  • Having undergone a previous endarterectomy;
  • Having severe congestive heart failure or unstable angina; and/or
  • Problems with other blood vessels in the head.


The goal of angioplasty is the restoration of adequate blood flow (revascularization) through the affected part of the body by enlarging the blood vessel from within.

To place a stent, the physician removes the angioplasty balloon catheter and inserts a new catheter on which a closed stent surrounds a deflated balloon. The stent-carrying catheter is advanced through the artery to the site of the blockage. The balloon is inflated, causing the stent to expand. The balloon is then deflated and the catheter withdrawn, leaving the stent in place. The stent in a carotid artery allows blood to flow to the brain.

The smooth lining of the arterial wall eventually grows back to cover the stent and secure it, so the stent will not dislodge. Stents are left in place permanently, and because they are made from stainless steel or metal alloys, they will not rust or deteriorate.


Risks commonly associated with carotid stenting may include:

  • Slight risk of stroke because of a loose piece of plaque or a blood clot blocking an artery during or immediately following surgery;
  • Abrupt closure of the artery after surgery;
  • Restenosis (the reoccurrence of plaque buildup) that occurs after a stent has been placed in the carotid artery, preventing future endarterectomy; or
  • Short periods of reduced blood pressure and heart rate that may occur, which is treated with medications.

Perhaps the most serious potential risks involved with carotid stenting are the risk of a disrupted plaque particle that breaks free from the site, called an embolism, and blocks an artery in the brain, causing a stroke. These risks are minimized using small filters called embolic protection devices in conjunction with angioplasty and stenting.

Hyper perfusion, or the sudden increased blood flow through a previously blocked carotid artery and into the arteries of the brain, may occur after stenting, and can cause a hemorrhagic stroke. While this is a risk of stenting, it is more likely to occur because of more invasive surgical procedures.

Carotid stenting, while generally safe and less invasive than endarterectomy, remains an evolving field. The first randomized controlled trial comparing surgery to carotid angioplasty and stenting was reported at the American Heart Association in November 2002, and showed significant benefits of stenting over surgery in reducing adverse events at one month in ‘high risk’ patients. More complete data and certain refinements of the devices used during the procedure are needed before stenting can be considered the primary treatment for blocked carotid arteries.

Source: NYU Medical Center

Carotid Stents vs Endarterectomy Surgery

For patients with blockages in the carotid artery that supplies blood to the brain, carotid artery stenting (a non-surgical therapy) may be linked to an increased risk of both short- and long-term adverse outcomes when compared with surgical therapy (carotid endarterectomy), as per a meta-analysis of previously published studies that was posted online today and will appear in the February 2011 print issue of Archives of Neurology, one of the JAMA/Archives journals.

“Carotid artery stenting has emerged as an alternative to carotid endarterectomy for the therapy of carotid artery occlusive disease,” the authors write as background information in the article. The treatmentwhich involves threading a catheter through the femoral (groin) artery to the carotid artery, inflating an angioplasty balloon to compress plaque and inserting a stent to keep the artery openis endorsed by the American Heart Association/American Stroke Association guidelines as a reasonable strategy and recommended by the European Society of Vascular Surgery in certain circumstances. However, its safety and efficacy as compared with carotid endarterectomy (surgery to remove the inner lining of the diseased blood vessel) is controversial.

Sripal Bangalore, M.D., M.H.A., of New York University School of Medicine, New York, and Harvard Clinical Research Institute, Boston, and his colleagues conducted a meta-analysis of 13 randomized clinical trials comparing the two therapys conducted through June 2010 and involving 7,477 patients with carotid artery disease. They assessed the risk of death, heart attack (myocardial infarction) and stroke within the periprocedural period (within 30 days of the procedure) as well as intermediate and long-term outcomes.

In the first 30 days, carotid artery stenting was linked to a 65 percent increased risk of death or stroke and a 67 percent increased risk of any stroke. However, the stent procedure was linked to a 55 percent lower risk of heart attack and 85 percent reduction in cranial nerve injury in this timeframe when compared with carotid endarterectomy.

Intermediate- to long-term outcomes were assessed using a composite involving death, any strokes or strokes on the side of the brain with carotid blockage (ipsalateral stroke) within 30 days or thereafter. Carotid artery stenting as compared with carotid endarterectomy was linked to a 19 percent increase in the risk of such an outcome, as well as an increased risk of various combinations of strokes, ipsilateral stroke and death. Stenting was also linked to an 180-percent increase in the risk of restenosis (repeat narrowing of the carotid artery).

“In this largest and most comprehensive meta-analysis to date using outcomes that are standard in contemporary studies, carotid artery stenting was linked to an increased risk of both periprocedural and intermediate to long-term outcomes, but with a reduction in periprocedural myocardial infarction and cranial nerve injury,” the authors conclude. “Strategies are urgently needed to identify patients who are best served by carotid artery stenting vs. carotid endarterectomy”.

(Arch Neurol. Published online October 11, 2010. doi:10.1001/archneurol.2010.262. Available pre-embargo to the media at

Editor’s Note: Senior author Dr. Bhatt has received research grants form AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis and The Medicines Company. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Meta-Analysis and Other Data Should Guide Personalized Medical Decisions for Each Patient

“What message can doctors take home from the past surgery vs. stenting horse races, from the numerous reports of results in patients not entered in trials, from the meta-analysis in this month’s Archives and from the recently published results of the Carotid Revascularization Endarterectomy vs. Stenting Trial?” write Louis R. Caplan, M.D, of Beth Israel Deaconess Medical Center, Boston, and Thomas G. Brott, M.D., of Mayo Clinic, Jacksonville, Fla., in an accompanying editorial.

“Both therapeutic procedures are effective. Both procedures showed a relatively low rate of serious complications. Surgery is superior concerning some outcomes; stenting seems to have advantages in others,” they write. In addition, “aggressive medical therapy of blood lipids, blood pressure and anti-platelets along with changes in lifestyle appears to be as good as or better than either surgery or stenting at stroke and myocardial infarcts prevention”.

“The past decades have produced three very effective therapysmedical, surgical and interventionalfor individuals with carotid artery disease,” they conclude. “The results and complications of each can be improved. We have learned much from the trials and they are a beacon to engender even further improvements. However, care of individual patients will always rest in the hands of a trained experienced doctor on one end of a stethoscope and a patient on the other end. Trials can enlighten that encounter but never replace it”.

(Arch Neurol. Published online October 11, 2010. doi:10.1001/archneurol.2010.268. Available pre-embargo to the media at

Carotid Angiography and Stenting Photo Gallery

Carotid Angiography

Carotid Artery Anatomy with Angiography

Carotid stents

In the past, vascular surgery was the standard of care for patients with carotid artery disease. Co-existing health conditions preventing patients to have surgical treatment led to the first carotid angioplasty and carotid stenting in 1994.

A carotid stent is a small wire mesh tube, inserted after angioplasty that acts as a scaffold to provide support inside the artery. Although carotid stenting remains investigational, several types of carotid stents are available to use during this procedure.

Patient post carotid surgery

Patient post carotid angioplasty & stent (no neck incision)

There are a variety of stents used for carotid stenting – below are three examples of carotid stents:

Caution: These devices are investigational in the United States and are limited by U.S. law to investigational use.

Endotex Carotid Stent

SMART Nitinol Stent

Guidant ACCULINK Carotid Stent System

Carotid stenting filter devices

Emboli protection devices have improved the safety of carotid stenting. Strokes that occur during, or in the first few minutes after, carotid angioplasty and stenting are caused by microemboli (tiny particles in the blood) dislodging and traveling to small distal blood vessels in the brain. Filter devices, combined with antiplatelet medication, provide protection against microemboli. The filter device’s microscopic-sized holes allow blood flow to continue as particles are captured in the device. At the end of the procedure, the filter is removed from the carotid artery along with captured debris. The rate of complications, including stroke, myocardial infarction (MI), and death, at the Cleveland Clinic Foundation are about 3 percent.

There are a variety of emboli protection devices (filters) used during carotid stenting – below are three examples:

Caution: These devices are investigational in the United States and are limited by U.S. law to investigational use.

Angioguard Emboli Capture Guidewire System

Guidant ACCUNET™ Embolic Protection System Filter Basket Specifications

FilterWire EX™ Carotid Wallstent® Monorail™

Filter device removed with microemboli captured

Carotid Angioplasty and Stenting – before and after angiography

Carotid angiography at baseline

Carotid angiography post angioplasty and stent

Mid-cerebral artery angioplasty and stenting – before and after angiography

Mid-cerebral artery angiography at baseline

Mid-cerebral artery angiography post angioplasty and stent, January 27, 2011, by Michael O’Riordan  —  (Dallas, Texas) — In the next 20 years, more than 40% of the US population is expected to have some form of cardiovascular disease, and this will triple the total direct medical costs of caring for hypertension, coronary heart disease, heart failure, stroke, and other forms of cardiovascular disease from the current $273 billion to more than $800 billion, according to a new policy statement from the American Heart Association (AHA) [1].

In addition, the AHA estimates that the prevalence of cardiovascular disease will increase by approximately 10% over the next 20 years given no changes to prevention and treatment trends. If some risk factors, such as diabetes and obesity, continue to increase rapidly, cardiovascular disease prevalence and associated costs might increase even more, write Dr Paul Heidenreich (Veteran Affairs Palo Alto Health Care System, CA) and colleagues in the report, published online January 24, 2011 in Circulation.

At present, cardiovascular disease is the leading cause of death in the US and accounts for 17% of overall healthcare expenditures. In the past, the medical costs of cardiovascular disease increased at an average annual rate of 6%, and this growth in costs has been associated with an increase in life expectancy. That said, there are “many opportunities to further improve cardiovascular health while controlling costs,” according to the AHA.

Cardiovascular Disease Is Largely Preventable

The latest 2030 prevalence estimates for hypertension, coronary heart disease, heart failure, and stroke are derived from the 1999–2006 National Health and Nutrition Examination Survey (NHANES) and Census Bureau population estimates for the years 2010 to 2030. Projections of the medical costs associated with cardiovascular disease used the 2001–2005 Medical Expenditure Panel Survey (MEPS) and did not double count expenditures resulting from individuals with multiple conditions.

By 2030, the prevalence of cardiovascular disease is expected to increase 9.9%, with the prevalence of heart failure and stroke increasing approximately 25%. Total direct costs will increase to $818 billion by 2030, according to the AHA estimates, and the total indirect cost to the US in terms of lost productivity is close to $275 billion.

Projections of Crude Cardiovascular Disease Prevalence (%)

Year All cardiovascular disease Hypertension Coronary heart disease Heart failure Stroke
2010 36.9 33.9 8.0 2.8 3.2
2015 37.8 34.8 8.3 3.0 3.4
2020 38.7 35.7 8.6 3.1 3.6
2025 39.7 36.5 8.9 3.3 3.8
2030 40.5 37.3 9.3 3.5 4.0
% change 9.9 9.9 16.6 25.0 24.9

Projected Direct Medical Costs of Cardiovascular Disease ($B)

Year All cardiovascular disease Hypertension Coronary heart disease Heart failure Stroke
2010 272.5 69.9 35.7 24.7 28.3
2015 358.0 91.4 46.8 32.4 38.0
2020 470.3 119.1 61.4 42.9 51.3
2025 621.6 155.0 81.1 57.5 70.0
2030 818.1 200.3 106.4 77.7 95.6
% change 200 186 198 215 238

Hypertension, the data show, has the greatest projected medical cost, in part because of the aging population, although the increase in prevalence and cost is not explained fully by age. Rising obesity rates are also contributing to the increasing rates of hypertension. The AHA notes that the downstream medical costs of high blood pressure–including its impact on cardiovascular disease and stroke–approximately double the cost of hypertension, making it a “particularly valuable target to modify the future total costs of cardiovascular disease.”‘

Offering up a glass-half-full take on the data, Heidenreich and colleagues write that it is “fortunate that cardiovascular disease is largely preventable,” and the healthcare system needs to focus on prevention and early intervention. The group highlights data from the Coronary Artery Risk Development in Young Adults (CARDIA) study that suggest cardiovascular disease prevention should begin earlier in life. In CARDIA, risk-factor levels in individuals younger than 30 years old were predictive of subclinical atherosclerosis 15 years later. The data, they write, also show that modest improvements in risk factors earlier in life have a larger impact than more substantial reductions later in life.

“In the public-health arena, more evidence-based effective policy, combined with systems and environmental approaches, should be applied in the prevention, early detection, and management of cardiovascular disease risk factors,” write the authors. “Through a combination of improved prevention of risk factors and treatment of established risk factors, the dire projection of the health and economic impact of cardiovascular disease can be diminished.”

Heidenreich reports no conflicts of interest. Disclosures for the coauthors are listed in the paper.

Tomatoes are one of the most common crops worldwide, and numerous previous studies document that the fruit contains many beneficial compounds that improve abnormalities of lipid metabolism. Teruo Kawada, from Kyoto University (Japan), and colleagues explored the role of tomato compounds in affecting dyslipidemia, a condition which is caused by an abnormal amount of lipids, such as cholesterol or fat, in the bloodstream.  The team analyzed 9-oxo-octadecadienoic acid, a compound abundantly found in tomato, and found it enhanced fatty acid oxidation and contributed to the regulation of hepatic lipid metabolism, via the peroxisome proliferator-activated receptor alpha (PPAR-alpha) pathway.  As a result, the researchers posit that 9-oxo-octadecadienoic acid exerts anti-dyslipidemia affects and may aid in  the prevention of vascular diseases

Read more……..

9-oxo-10(E),12(E)-octadecadienoic acid derived from tomato is a potent PPAR agonist to decrease triglyceride accumulation in mouse primary hepatocytes

1.                               Young-Il Kim1,

2.                               Shizuka Hirai1,

3.                               Haruya Takahashi1,

4.                               Tsuyoshi Goto1,

5.                               Chie Ohyane1,

6.                               Taneaki Tsugane2,

7.                               Chiaki Konishi3,

8.                               Takashi Fujii3,

9.                               Shuji Inai3,

10.                            Yoko Iijima4,

11.                            Koh Aoki4,

12.                            Daisuke Shibata4,

13.                            Nobuyuki Takahashi1,

14.                            Teruo Kawada1,*


Scope: Tomato is one of the most common crops worldwide and contains many beneficial compounds that improve abnormalities of lipid metabolism. However, the molecular mechanism underlying the effect of tomato on lipid metabolism is unclear. It has been commonly accepted that peroxisome proliferator-activated receptor (PPAR) is one of the most important targets for ameliorating abnormalities of lipid metabolism. Therefore, we focused on the activation of PPAR and attempted to detect active compounds activating PPAR in tomato.

Methods and results: To identify such active compounds, we screened fractions of tomato extracts using PPAR luciferase reporter assay. One fraction, rechromatographed-fraction eluted in 57 min (RF57), significantly increased PPAR reporter activity, in which a single compound is detected by LC/MS analysis. On the basis of LC/MS and NMR analyses, we determined the chemical structure of the active compound in RF57 as 9-oxo-10(E),12(E)-octadecadienoic acid (9-oxo-ODA). The RF57 fraction significantly increased the mRNA expression levels of PPAR target genes involved in fatty acid oxidation and O2 consumption in mouse primary hepatocytes. Furthermore, RF57 inhibited cellular triglyceride accumulation in the hepatocytes.

Conclusion: These findings suggest that tomatoes containing 9-oxo-ODA that acts on PPAR are valuable for ameliorating abnormalities of lipid metabolism.