• Angioplasty
• Coronary Artery Disease
• Peripheral Vessel Disease
• Kidney Disease
• Hypertension
• Diabetes Mellitus
• Macular Degeneration
• Lung Fibrosis

VBI RESEARCH

New  Clinical Cardiovascular

Peripheral Artery Disease (claudication; leg pain; critical limb ischemia)

Disease incidence and description:  Intermittent claudication (muscle pain) affects more than 5 percent of people over 50 years of age in the United States and Europe and has a variable outcome with symptoms progressing rapidly in 25 percent of patients and almost ten percent requiring amputations within five years. Progressive deterioration to rest pain or gangrene occurs in about 20 percent of all patients with intermittent claudication. The life expectancy of amputees is less than five years. The main risk factors include diabetes, smoking, family history, high cholesterol, and hypertension.

Ongoing Treatments:  PAD is treated conventionally in two ways (1) bypass surgery, accounting for up to 50,000 procedures in the United States annually, and (2) angioplasty performed approximately 200,000 times per year. Of these, 85,000 patients have PAD below the knee and experience a 75 percent restenosis rate, 60,000 patients with femoral PAD experience a 50 percent restenosis rate, and 55,000 patients with iliac PAD experience 5 percent restenosis. If surgical procedures fail there are few remaining options. 150,000 patients require lower limb amputation for critical limb ischemia in the United States annually. Perioperative mortality is five to ten percent for below-the-knee amputation, and 15 to 20 percent for above-the-knee amputation. Even when these patients survive surgery, nearly 40 percent will die within two years of the first amputation. A second amputation is required in 30 percent of cases, and full mobility is achieved in only 50 percent of patients who have above-the-knee amputation. There are no effective drug treatments.

Miami VBI Treatment:  The efforts of a twelve year research program on peripheral artery disease are now bringing a new technology to the clinic that may be effective for all forms of this disease. This program combines optimized gene and stem cell-based therapies to create a product that effectively stimulates the growth of new blood vessels in ischemic limbs and has the potential to reverse and perhaps cure peripheral artery disease. The treatment is called Therapeutic Angiogenesis (TA). The treatment has been tested pre-clinically and pilot clinical tests are anticipated to begin within the next twelve months.

Coronary Artery Disease (angina; chest pain; arm pain, heart attack)

Disease incidence and description:  Coronary artery disease (CAD) continues to be the leading cause of morbidity and mortality in North America and Europe. This is despite significant advances in interventional cardiology and pharmacological treatments. Currently more than twelve million people in the United States have CAD, and more than seven million have had a myocardial infarction (MI). Chronic stable angina is the initial manifestation of CAD in approximately half of all presenting patients, and it is estimated that 16.5 million Americans currently have stable angina. CAD is often associated with diabetes, obesity, hypertension and old age.

Ongoing Treatments:  Because of the vital function of the heart, CAD is more immediately life threatening than peripheral artery disease. CAD is treated surgically and pharmacologically. A plethora of expensive prescription drugs are available and many patients are on multiple life-long drug regimes. Surgical interventions are also increasing, there were two million inpatient cardiac catheterizations, and more than one million angioplasty and bypass procedures performed in 2003 in the United States. The economic cost of CAD in the United States is estimated to be greater than $120 billion per year. As many as ten percent of patients with heart disease are not candidates for surgery and are not responsive to pharmacotherapy.

Miami VBI Treatment:  Like PAD, CAD is also a target for TA and the product described above also has direct application for CAD. Angina, or chest pain. is usually the result of insufficient blood supply to a region of the heart. The Miami Vascualr Biology Institute TA procedure works by delivering the patients own modified stem cells to the region of the heart that is causing problems. This results in the production of new blood vessels in that region that can re-supply blood and oxygen, effectively reversing the problem. TA for CAD is still in the preclinical phase of testing.

 

Discovery  Clinical Cardiovascular

Vascular dysfunction  is a major component of CAD and PAD. Diseased or aged vessels are unable to respond normally to physiological signals, they loose the flexibility of a young healthy vessel and become “hardened” so that communications between the vessel wall and the blood including pressure and flow are lost. This places increased stress on the heart and promotes heart failure. Vascular dysfunction may promote angina, shortness of breath symptoms and arm pains.

Miami Vascular Biology Institute Research:  As part of continuing investigations into risk factors associated with heart and vascular disease the aging research program has investigated the roles of stem cells from the bone marrow in promoting, and potentially treating blood vessel dysfunction. This program, directed by Aitouche Abdelouahab, Ph.D., involves transplanting sections of blood vessels between young and old subjects and analyzing stem cell migration and vessel function types. Specifically the studies involved two key cell types called endothelial cells and vascular smooth muscle cells that surround the lumen of the blood vessel tube. The smooth muscle plays an important role in determining the diameter of the blood vessel, if the smooth muscle contracts, vessel diameter decrease and blood pressure may rise, conversely when smooth muscle relaxes, vessel diameter increases and blood pressure is reduced. In the coronary vasculature, signals from the endothelial cells that are in direct contact with the blood normally control the contractions of the smooth muscle so that blood pressure is precisely controlled. This communication system begins to fail in patients with CAD and especially in elderly patients. By using aging models and vessel transplants we have very recently discovered that stem cells in the bone marrow play a central part in determining the success or failure of the endothelial smooth muscle communication network. These studies will be extended to backgrounds of diabetes and clinical trials lead by Ariel Zisman, M.D. are in process to assess endothelial dysfunction directly in patients.

Hypertension  is a first line risk factor for cardiovascular and chronic kidney diseases. Hypertension has reached epidemic proportions in the United States and is often associated with obesity, diabetes, smoking, and sedentary lifestyles. Hypertension often leads to dysfunction of blood vessel walls that can result in breathlessness and chest pain especially during or after exercise. This promotes atherosclerosis, coronary artery disease, myocardial ischemia and heart and kidney failure. Research lead by Leopoldo Raij, M.D., an internationally recognized authority on hypertension, is working to identify the targets and causes of blood vessel dysfunction in patients with hypertension, in particular the roles played by cholesterol, smoking, menopause, obesity, and diabetes. This research, some of which already involves human patients, is focused on the development of better drugs, possibly add-ons or improved statins, to combat hypertension, atherosclerosis, endothelial dysfunction, and kidney failure.

Angioplasty  involves the mechanical clearing of an occluded blood vessel by insertion of a catheter into the disease vessel to compress the plaque. It is a common procedure for treating chest pain caused by coronary artery disease. A frequent problem associated with angioplasty is the recurrence of plaque at the same site so that the procedure must be repeated as chest pain returns. Placement of drug eluting stents reduces but does not eliminate this problem. A research tem lead by Hong Yu, Ph.D. is using grafts engineered with thrombolytic enzyme genes inserted into a coat of vascular cells to provide long-term protection against thrombosis. Super-engineered grafts are also being developed to deliver therapeutic genes including erythropoietin, insulin, and factor IX to the blood stream.

Macular degeneration, research into age-related macular degeneration (ARMD), the leading cause of blindness in the elderly population have strong clinical and basic ingredients. The Vascular Biology Institute is focused on identifying the molecular pathways that initiate ARMD, identifying cellular targets, and developing novel therapeutic targets. Current results indicate that oxidative stress and inflammation interact negatively with specific proteins that surround the RPE membranes triggering a negative cascade that ultimately causes cell death and loss of function of the retina. Antioxidant therapy, including estrogen may alleviate progression of ARMD. These studies include clinical and preclinical research projects.

Kidney disease, The Vascular Biology Institute has a multidisciplinary approach to kidney disease with an emphasis on the early stages involving the development of glomerulosclerosis. Mesangial cells (glomerula smooth muscle), circulating stem cells and hormone interactions (estrogen) are the main focus of these studies. Projects are currently in the discovery phase and are strongly integrated with diabetes, including insulin resistance and its consequences for the kidney and the heart.