Mitochondrial Function in Transthyretin Amyloidosis
Mitochondrial Function in Transthyretin Amyloidosis
Hereditary (familial) amyloidosis arising from the misfolding of a mutated or variant
 transthyretin, is the most frequent form of amyloid cardiomyopathy in the Caribbean basin.
 Affected organs invariably harbor extracellular amyloid deposits in the myocardium.
 Circulating or pre-fibrillar amyloidogenic proteins are implicated in the disruption of cell
 function. The investigators aim is to demonstrate that transthyretin mediated amyloid disease
 alter the mitochondrial function of cardiac cells.
Systemic amyloidosis are a family of diseases induced by misfolded and/or misassembled
 proteins. Extracellular deposits of these proteins disrupt vital organ function. Two types of
 amyloid commonly infiltrate the heart: immunoglobulin light-chain amyloid and transthyretin
 (TTR) amyloid. Among the TTR variants that predominantly target the heart, the valine to
 isoleucine substitution at position 122 (V122I or Ile122) is the most common. This TTR
 variant is responsible for the most frequent form of amyloid cardiomyopathy in the Caribbean
 basin. Increasingly study data supports a central role for circulating or pre-fibrillar
 amyloidogenic proteins in the disruption of cardiac function in TTR mediated amyloid disease.
 In vivo exposure of cultured cardiomyocytes to pre-fibrillar an amyloidogenic proteins
 stimulate the production of reactive oxygen species and disrupts calcium fluxes. (Recent
 studies indicate that pre-fibrillar amyloidogenic proteins may also induce apoptosis through
 the mitochondrial pathway, eventually leading to cardiac cell injury). Hence, growing
 evidence suggests that end-organ damage by pre-fibrillar TTR amyloid may be related to
 mitochondrial dysfunction. Diagnosis of cardiac amyloidosis can be based on invasive heart
 biopsies or a non-invasive approach including identification of amyloid tissue deposits from
 abdominal fat biopsies. The investigators aim is to demonstrate that transthyretin mediated
 amyloid disease alters the mitochondrial function of subcutaneous abdominal adipocytes.

 The investigators objective is to study mitochondrial respiration assessed by oxygraphy in
 fragments of subcutaneous abdominal fat biopsies performed for diagnosis of TTR amyloidosis.
 Mitochondrial respiration will be evaluated in the absence and in the presence of ADP.

 Follow the evaluation of mitochondrial respiration. So, no patient follow-up will be
 performed.
Inclusion Criteria:

 -  Have a parietal thickness measuring more than 15 mm on the echocardiography or have
 structural and echogenicity abnormalities characteristic of cardiac amyloidosis,

 -  Live in Martinique,

 -  Accept the use of the residues coming from biopsies of the subcutaneous abdominal
 adipose tissue performed during the medical care.

 Exclusion Criteria:

 -  Be under 18 years old,

 -  Have a contraindication to subcutaneous biopsy,

 -  Be allergic to local anesthetics,

 -  Pregnant or nursing woman,

 -  Have a cardiovascular disease suggesting a secondary cardiac disease, such as
 documented severe hypertension, valvular stenosis, or a known familial cardiomyopathy,

 -  Be major under guardianship / curatorship or deprived of liberty,

 -  Not be able to answer to a simple administrative questionnaire or to give freely its
 non-opposition.