Exploring the potential of cholesterol-lowering drugs for patients with systemic sclerosis

May 25, 2006

Systemic sclerosis (SSc), also known as scleroderma, is an uncommon and confounding disease characterized by excessive fibrous tissue formation and vascular abnormalities. Primarily affecting the small arties, SSc decreases blood flow to the body's extremities. This can lead to Raynaud's phenomenon, a condition that causes the hands and feet to feel extremely cold and numb; ulcers on the fingers and toes; and gangrene. SSc can also restrict blood flow to internal organs, resulting in lung, kidney, and heart damage. While its cause and cure have yet to be found, SSc is generally viewed and treated as an autoimmune inflammatory disorder.

Researchers in Japan recently proposed a different theory: the root of SSc may be defective vasculogenesis, the process of forming new blood vessels by producing new cells in the blood vessel lining. In the June 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), Dr. Masataka Kuwana and colleagues at the Keio University School of Medicine in Tokyo share the results of an experiment to affirm their hypothesis and test a novel treatment strategy. Their objective: to determine the effectiveness of one of the most popular and potent cholesterol-lowering drugs - atorvastatin, marketed under the brand name Lipitor - for increasing blood flow and improving the symptoms of SSc.

The study focused on 14 women, between ages 36 and 75, with a confirmed diagnosis of SSc. Disease duration ranged from 13 months to 21 years. All the patients were treated with 10 milligrams of atorvastatin per day for 12 weeks; all but one participated in a follow up 4 weeks after. At the time of entry, all the patients had active Raynaud's phenomenon, and 2 had digital ulcers. For the study's duration, all patients continued their routine course of treatment, from low-dose aspirin to low-dose prednisolone.

At pre-treatment, at weeks 4, 8, and 12 during treatment, and at 4 weeks post-treatment, all the patients were evaluated for SSc symptoms. What's more, and most significant, each patient was assessed, using rigorously developed assay systems, for their absolute number of circulating endothelial precursors (CEPs). Vasculogenesis requires the recruitment of CEPs from bone marrow to form blood vessels when there are no pre-existing ones. This study's ultimate goal was to evaluate whether statins work to treat SSc by increasing patient's production of strong, blood vessel-building CEPs.

For the 13 patients who completed the 12 weeks of therapy, atorvastatin yielded a 1.7 to 8-fold increase in the number of CEPs. However, for 8 patients, 62 percent of the group, CEP levels peaked during treatment, either at week 4 or week 8, and gradually decreased thereafter. Even for the 5 patients who experienced continual gains in CEP levels while taking atorvastatin, the numbers did not reach the levels seen in healthy individuals. For all patients, CEP counts returned to within baseline counts by the follow up session. All the patients experienced improvements in Raynaud's phenomenon activity while taking atorvastatin. Symptoms generally returned to within baseline levels after discontinuation of the drug.

As this study demonstrates, atorvastatin is capable of stimulating CEP production in SSc patients. But its effects are limited. "Although the results of this preliminary study are encouraging," Dr. Kuwana notes, "further multicenter, placebo-controlled trails involving a large number of SSc patients are necessary to confirm the clinical benefit of statins in SSc patients."
Article: "Increase in Circulating Endothelial Precursors by Atorvastatin in Patients With Systemic Sclerosis," Masataka Kuwana, Junichi Kaburaki, Yuka Okazaki, Hidekata Yasuoka, Yutaka Kawakami, and Yasuo Ikeda, Arthritis & Rheumatism, June 2006, 54:6, pp. 1946-1951.


Related Blood Vessels Articles from Brightsurf:

Biofriendly protocells pump up blood vessels
In a new study published today in Nature Chemistry, Professor Stephen Mann and Dr Mei Li from Bristol's School of Chemistry, together with Associate Professor Jianbo Liu and colleagues at Hunan University and Central South University in China, prepared synthetic protocells coated in red blood cell fragments for use as nitric oxide generating bio-bots within blood vessels.

Specific and rapid expansion of blood vessels
Upon a heart infarct or stroke, rapid restoration of blood flow, and oxygen delivery to the hypo perfused regions is of eminent importance to prevent further damage to heart or brain.

Flexible and biodegradable electronic blood vessels
Researchers in China and Switzerland have developed electronic blood vessels that can be actively tuned to address subtle changes in the body after implantation.

Lumpy proteins stiffen blood vessels of the brain
Deposits of a protein called ''Medin'', which manifest in virtually all older adults, reduce the elasticity of blood vessels during aging and hence may be a risk factor for vascular dementia.

Cancer cells take over blood vessels to spread
In laboratory studies, Johns Hopkins Kimmel Cancer Center and Johns Hopkins University researchers observed a key step in how cancer cells may spread from a primary tumor to a distant site within the body, a process known as metastasis.

Novel function of platelets in tumor blood vessels found
Scientists at Uppsala University have discovered a hitherto unknown function of blood platelets in cancer.

Blood vessels can make you fat, and yet fit
IBS scientists have reported Angiopoietin-2 (Angpt2) as a key driver that inhibits the accumulation of potbellies by enabling the proper transport of fatty acid into general circulation in blood vessels, thus preventing insulin resistance.

Brothers in arms: The brain and its blood vessels
The brain and its surrounding blood vessels exist in a close relationship.

Feeling the pressure: How blood vessels sense their environment
Researchers from the University of Tsukuba discovered that Thbs1 is a key extracellular mediator of mechanotransduction upon mechanical stress.

Human textiles to repair blood vessels
As the leading cause of mortality worldwide, cardiovascular diseases claim over 17 million lives each year, according to World Health Organization estimates.

Read More: Blood Vessels News and Blood Vessels Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.