Collagen and elastin metabolism in hypertensive pulmonary arteries of rats.

Abstract

We evaluated the processes controlling the accumulation of collagen and elastin in main pulmonary arteries of rats during an episode of hypoxic pulmonary hypertension. Explant cultures of main pulmonary arteries were incubated with [3H]proline to measure collagen and protein synthesis and percent collagen synthesis. Elastin synthesis was measured by [14C]valine incorporation into insoluble elastin. Relative collagen synthesis increased twofold (from 1.1 +/- 0.2 x 10(3) to 2.0 +/- 1.0 x 10(3) disintegrations per minute [14C]hydroxyproline/vessel/hr/mg protein), relative collagen synthesis doubled (from 2% to 4-5% of total protein synthesis), and elastin synthesis increased ninefold (from 0.4 +/- 0.2 x 10(4) to 3.6 +/- 0.6 x 10(4) dpm [14C]valine/vessel/hr/mg protein) in early hypertension. The level of pro alpha l(I) collagen RNA paralleled the relative collagen synthetic rate during the study period. Within 7 days of recovery from hypoxia, collagen and elastin contents were normal. We conclude that collagen and elastin in main pulmonary arteries are synthesized rapidly during an episode of hypoxic pulmonary hypertension and that collagen and elastin are rapidly removed from the hypertensive vessel during normoxic recovery.

The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension

“…With recovery, the PA pressures of the Col1a1 ϩ/ϩ mice returned to normal levels, as previously shown to occur in rats (26,27,38). In the Col1a1 R/R mice, the mean PA pressures after recovery tended to be higher than normal levels, which supports the important roles of both smooth muscle cell (SMC) apoptosis and collagen degradation in recovery (40).…”

“…In addition to decreasing arterial stretch and increasing mid-to-high-strain modulus, hypoxia induced collagen accumulation in Col1a1 ϩ/ϩ mice and tended to increase collagen in the Col1a1 R/R mice; increases in collagen with HPH were found previously in mice (20,21) and rats (38). We hypothesized that, while breakdown of most extracellular matrix proteins (including collagen type I) would occur in Col1a1 ϩ/ϩ PAs during recovery, the resistance of collagen type I to degradation in the Col1a1 R/R mice would prevent the reduction in PA collagen content in this strain and cause persistent PA stiffening.…”

“…Differences between the biochemical assay used here and previous histological measurements could be due to structural changes in elastic lamina that alter histological appearance without changing content. Prior studies using biochemical methods to determine the effect of chronic hypoxia on elastin content in extralobar arteries are not in agreement; using an assay for desmosine, Merklinger et al (31) found no change, whereas Poiani et al (38) found an increase.…”

The role of vascular injury and hemodynamics in rat pulmonary artery remodeling.

“…The reason for the difference between human and experimental patterns of pulmonary vascular remodeling has not been determined. Injury appears to be important since these models require a persistent vascular insult, such as chronic hypoxia in the rat (8) and newborn calf (9,10), monocrotaline intoxication in the rat (11), or chronic air emboli in the sheep (12), to initiate and maintain remodeling. Thus, although both pulmonary and systemic (13,14) arteries appear to require injury to initiate remodeling, whether alterations in pulmonary artery hemodynamics would lead to neointimal formation in these animal models is unknown.…”

Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension

“…Structural abnormalities include muscularization of normally nonmuscular peripheral arteries, medial hypertrophy of more proximal muscular arteries associated with hypertrophy and hyperplasia of smooth muscle cells (SMCs), and increases in extracellular matrix (ECM) proteins, most notably collagen and elastin [1,2].…”