Iraklis I. Pipinos

Curriculum Vitae

Associate Professor
M.D., Ph.D., Both at University of Crete School of Medicine
Specialty: Vascular Surgery
Major Interest: Myopathy of Peripheral Arterial Disease

The laboratory of Drs. Pipinos and Casale is a highly interdisciplinary environment.  The major focus of the laboratory is the development of regenerative medicine strategies for skeletal muscle tissue in the legs of patients suffering from peripheral arterial disease (PAD).  PAD afflicts 5% of the US population older than 55 years of age and develops along with hardening (atherosclerosis) of the arteries of the legs.  PAD is a chronic condition that decreases the blood supply to the legs producing significant damage to the muscle.  Patients with PAD limp and can only walk very short distances because the muscle in their legs is damaged and their legs hurt.  Our laboratory evaluates the mechanisms that may produce the leg dysfunction of claudication and its successful completion can ultimately improve patient prognosis and produce significant new diagnostic and treatment strategies for the care of claudicating patients.  Our research group is involved in multiple projects and involve the combined efforts of biomechanists, life scientists, biomedical engineers, physicians, veterinarians, and a strong technical support staff.

Our principal research interests include:

  • Regeneration of adult skeletal muscle with the use of exercise, medications, adult stem cells and revascularization operations
  • Mitochondrial dysfunction, oxidative damage and inflammation in the leg muscle of patients with PAD
  • Atrophy in the leg muscle of patients with PAD
  • Biomechanical analysis of the gait of PAD patients
  • Developmental Biology and its role in Regenerative Medicine

Proposed pathway for the pathogenesis of PAD manifestations.  The fundamental problem in PAD is obviously the presence of arterial occlusive disease.  Arterial stenoses and occlusions produce effort-induced cycles of ischemia and reperfusion.  These cycles initiate a combination of oxidative stress and inflammation, which sets in motion a cascade of injury to muscle cells and their organelles along with cellular apoptosis and necrosis.  Key players in the chronic phase of this process are dysfunctional mitochondria that, through multilevel failure in their roles as energy, oxygen radical species, and apoptosis regulators, produce and sustain a myopathy with progressive decline in muscle performance.  This myopathy is the better explored component of this process in PAD limbs, and its nature is the main focus of the present review.  However, there is increasing evidence demonstrating that the injury route expands to involve every structure in the leg including nerves, skin, and subcutaneous tissues.  Claudication, rest pain, and tissue loss then emerge as the external manifestations of ongoing tissue functional deterioration and injury.  PAD indicates peripheral arterial occlusive disease; ETC, electron transport chain. 

 Recent publications:

  1. Pipinos II, Shepard AD, Anagnostopoulos PV, Katsamouris A, Boska MD. 31P Nuclear Magnetic Resonance Spectroscopy reveals evidence for a primary dysfunction of mitochondria in claudicating muscle. J Vasc Surg 2000 May;31(5):944 952. (no PMID number found)
  2. Pipinos II, Sharov VG, Shepard AD, Anagnostopoulos PV, Katsamouris A, Todor A, Filis KA, Sabbah HN. Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease. J Vasc Surg. 2003 Oct;38(4):827-32. PMID: 14560237
  3. Pipinos II, Judge AR, Zhu Z, Selsby JT, Swanson SA, Johanning JM, Baxter BT, Lynch TG, Dodd SL. Mitochondrial defects and oxidative damage in patients with peripheral arterial disease. Free Radic Biol Med. 2006 Jul 15;41(2):262-9. PMID: 16814106
  4. Pipinos II, Judge AR, Selsby JT, Zhu Z, Swanson SA, Nella AA, Dodd SL. The myopathy of peripheral arterial occlusive disease: Part 2. Oxidative Stress, Neuropathy, and Shift in Muscle Fiber Type. Vasc Endovascular Surg. 2008 Apr-May;42(2):101-12. PMID: 18390972
  5. Pipinos II, Swanson SA, Zhu Z, Nella AA, Weiss DJ, Gutti TL, McComb RD, Baxter BT, Lynch TG, and Casale GP. Chronically ischemic mouse skeletal muscle exhibits myopathy in association with mitochondrial dysfunction and oxidative damage. Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R290-6. PMID: 18480238